Compositions for delivery of plasmodium antigens and related methods

Abstract

The present disclosure provides compositions (e.g., pharmaceutical compositions) for delivery of malarial protein antigens and related technologies (e.g., components thereof and / or methods relating thereto). Among other things, the present disclosure provides polyribonucleotides encoding malarial protein antigens.

Description

COMPOSITIONS FOR DELIVERY OF PLASMODIUM ANTIGENS AND RELATED METHODSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Application Serial No. 63 / 515,079, filed July 21, 2023, the entirety of which is incorporated herein by reference.BACKG ROUND

[0002] Malaria is a mosquito-borne infectious disease caused by protozoan parasites of the Plasmodium genus.According to the World Health Organization, an estimated 3.4 billion people in 92 countries are at risk of being infected with the malaria parasite and developing disease.SUMMARY

[0003] The present disclosure provides technologies (e.g., compositions, methods, etc) for delivery of Plasmodium antigens (also referred to herein as "malaria antigens”). In one aspect, provided herein is a polyribonucleotide encoding a polypeptide, wherein the polypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof. In some embodiments, a portion is an antigenic portion.

[0004] In some embodiments, a polyribonucleotide as provided herein is an isolated polyribonucleotide. In some embodiments, a polyribonucleotide as provided herein is an engineered polyribonucleotide. In some embodiments, a polyribonucleotide as provided herein is a codon-optimized polyribonucleotide.

[0005] In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise: (i) one or more Plasmodium reticulocyte-binding protein homolog 5 (Rh5) polypeptides or antigenic portions thereof; (ii) one or more Plasmodium Cysteine-Rich Protective Antigen (CyRPA) polypeptides or antigenic portions thereof; (iii) one or more Plasmodium Rh5-interacting Protein (Ripr) polypeptides or antigenic portions thereof; (iv) one or more Plasmodium P113 polypeptides or antigenic portions thereof; (v) one or more Plasmodium thrombospondin-related apical merozoite protein (TRAMP) polypeptides or antigenic portions thereof; or (vi) one or more Plasmodium cysteine-rich small secreted protein (CSS) polypeptides or antigenic portions thereof.

[0006] In some embodiments, a polyribonucleotide encodes a polypeptide, wherein the polypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof. In some embodiments, a polyribonucleotide encodes a polypeptide, wherein the polypeptide comprises one or more Plasmodium reticulocytebinding protein homolog 5 (Rh5) polypeptides or antigenic portions thereof.

[0007] In some embodiments, one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof comprise one or more antigenic portions of Plasmodium Rh5. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise one or more ordered domains of Rh5. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise two ordered domains of Rh5. In some embodiments, two ordered domains of Rh5 are directly adjacent to one another. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a cysteine at position 203, 329, or both, as numbered according to SEQ ID NO: 1. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise: (i) an amino acid sequence according to SEQ ID NO: 118, 119, 124, or 126, (ii) an amino acid sequence according to SEQ ID NO: 120 or 128, or (iii) a combination thereof.RECTIFIED SHEET (RULE 91) ISA / EP

[0008] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a tyrosine at position 203, 329, or both, as numbered according to SEQ ID NO: 1. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise: (i) an amino acid sequence according to SEQ ID NO: 121, 122, 125, or 127, (ii) an amino add sequence according to SEQ ID NO: 123 or 129, or (iii) a combination thereof. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a tyrosine at position 203, as numbered according to SEQ ID NO: 1. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a tyrosine at position 329, as numbered according to SEQ ID NO: 1.

[0009] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise one, two, three, or four N-linked glycosylation sites. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise two N-llnked glycosylation sites. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a substitution of NX[T / S] to QX[T / S] and / or a substitution of NX[T / S] to NXA. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise: (i) an amino add sequence according to SEQ ID NO: 124, 125, 126, or 127, (ii) an amino add sequence according to SEQ ID NO: 128 or 129, or (ii) a combination thereof.

[0010] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino acid substitution that prevents glycosylation at position 214, as numbered according to SEQ ID NO: 1. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino acid substitution that prevents glycosylation at position 297, as numbered according to SEQ ID NO: 1. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino add substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0011] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a PMX deavage site. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino add sequence according to SEQ ID NO: 118, 121, 124, or 125. In some embodiments, one or more Plasmodium Rh5 antigenic portions do not comprise a PMX cleavage site.

[0012] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino add sequence according to SEQ ID NO: 119, 122, 126, or 127. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise: (i) an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 130, (ii) an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 118, 119, 121, 122, 124, 125, 126, or 127, (iii) an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 131, (iv) an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 120, 123, 128, or 129, or (v) a combination thereof.

[0013] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise (i) an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 118, 119, 121, 122, 124, 125, 126, or 127, (ii) an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 120, 123, 128, or 129, or (iii) a combination thereof. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise: (i) an amino add sequence according to SEQ ID NO: 121 or 122, and (ii) an amino add sequence according to SEQ ID NO: 120. In some embodiments, one or more PlasmodiumRh5 antigenic portions comprise: (i) an amino acid sequence according to SEQ ID NO: 125 or 127, and (ii) an amino add sequence according to SEQ ID NO: 120 or 128.

[0014] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino acid sequence with at least 85% sequence identity to an amino add sequence of positions 26-363 of SEQ ID NO: 94, 95 or 99. In some embodiments, one or more PlasmotSum Rh5 antigenic portions comprise an amino acid sequence with at least 85% sequence identity to an amino add sequence of positions 26-526 of SEQ ID NO: 89. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino add sequence of positions 26-363 of SEQ ID NO: 94. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino add sequence of positions 26-363 of SEQ ID NO: 95. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino acid sequence of positions 26-363 of SEQ ID NO: 99. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise an amino add sequence of positions 26-526 of SEQ ID NO: 89. In some embodiments, one or more Plasmodium Rh5 antigenic portions do not comprise a disordered domain of Rh5. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a PMX cleavage site. In some embodiments, a PMX deavage site comprises or consists of an amino acid sequence of NFLQ.

[0015] In some embodiments, one or more Plasmodium Rh5 Invasion complex antigens comprise a Plasmodium CyRPA polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 Invasion complex antigens comprise an antigenic portion of Piasmocfium CyRPA.

[0016] In some embodiments, a Plasmodium CyRPA antigenic portion comprises an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 133. In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of an amino add sequence of SEQ ID NO: 133. In some embodiments, a Plasmodium CyRPA antigenic portion comprises an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 169. In some embodiments, a Plasmodium antigenic portion comprises or consists of an amino acid sequence of SEQ ID NO: 169.

[0017] In some embodiments, a Plasmodium CyRPA antigenic portion comprises one, two, or three N-llnked glycosylation sites. In some embodiments, a Plasmodium CyRPA antigenic portion comprises an amino add substitution at one or more N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a substitution of NX[T / S] to QX[T / S]. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a substitution of NX[T / S] to NXA. In some embodiments, a Plasmodium CyRPA antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0018] In some embodiments, a Plasmodium CyRPA antigenic portion comprises an asparagine at position 145, position 322, position 338, or a combination thereof, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a glutamine at position 145, position 322, position 338, or a combination thereof, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a glutamine at position 145, position 322, and position 338, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of an amino acid sequence of SEQ ID NO: 134. In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of an amino add sequence of SEQ ID NO: 170.

[0019] In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise a Plasmodium Pl 13 polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise an antigenic portion of Plasmodium Pl 13.

[0020] In some embodiments, a Plasmodium P113 antigenic portion comprises an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 135. In some embodiments, a Plasmodium P113 antigenic portion comprises or consists of an amino acid sequence of SEQ ID NO: 135.

[0021] In some embodiments, a Plasmodium P113 antigenic portion comprises one, two, three, four, five, six, seven, or eight N-linked glycosylation sites. In some embodiments, a Plasmodium P113 antigenic portion comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, a Plasmodium P113 antigenic portion comprises a substitution of NX[T / S] to QX[T / S], In some embodiments, a Plasmodium P113 antigenic portion comprises a substitution of NX[T / S] to NXA. In some embodiments, a Plasmodium P113 antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation.

[0022] In some embodiments, a Plasmodium P113 antigenic portion comprises an asparagine at position 207, position 268, position 317, position 360, position 661, position 697, position 779, position 876, or a combination thereof, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium Pl 13 antigenic portion comprises a glutamine at position 207, position 268, position 317, position 360, position 661, position 697, position 779, position 876, or a combination thereof, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium Pl 13 antigenic portion comprises a glutamine position 207, position 268, position 317, position 360, position 661, position 697, position 779, and position 876, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium P113 antigenic portion comprises or consists of an amino add sequence of SEQ ID NO: 136.

[0023] In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise a Plasmodium Rlpr polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise an antigenic portion of Plasmodium Rlpr.

[0024] In some embodiments, a Plasmodium Rlpr antigenic portion comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 178. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 177. In some embedments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 177.

[0025] In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 176. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 175. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 175.

[0026] In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 174. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino acid sequence according to SEQ ID NO: 174.

[0027] In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 190. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino acid sequence according to SEQ ID NO: 190.

[0028] In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 171. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino acid sequence according to SEQ ID NO: 171.

[0029] In some embodiments, a Plasmodium Ripr antigenic portion comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven or twelve N-llnked glycosylation sites. In some embodiments, a Plasmodium Ripr antigenic portion comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, a Plasmodium Ripr antigenic portion comprises a substitution of NX[T / S] to QX[T / S]. In some embodiments, a Plasmodium Ripr antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation.

[0030] In some embodiments, a Plasmodium Ripr antigenic portion comprises an asparagine at position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 2. In some embodiments, a Plasmodium Ripr antigenic portion comprises a glutamine at position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 2. In some embodiments, a Plasmodium Ripr antigenic portion comprises a glutamine at position 646, position 964, and position 1021, as numbered according to SEQ ID NO: 2. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 190.

[0031] In some embodiments, a Plasmodium Ripr antigenic portion comprises an asparagine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 2. In some embodiments, a Plasmodium Ripr antigenic portion comprises a glutamine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 2. In some embodiments, a Plasmodium Ripr antigenic portion comprises a glutamine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, position 1021, as numbered according to SEQ ID NO: 2. In some embodiments, a Plasmodium Ripr antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 171.

[0032] In some embodiments, a Plasmodium Ripr antigenic portion comprises a PMX cleavage site. In some embodiments, a PMX deavage site comprises or consists of an amino acid sequence of SMLE.

[0033] In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise a Plasmodium TRAMP polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise an antigenic portion of Plasmodium TRAMP.

[0034] In some embodiments, a Plasmodium TRAMP antigenic portion comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 179. In some embodiments, a PfasmodiumTRMAP antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 179.

[0035] In some embodiments, a Plasmodium TRAMP antigenic portion comprises one, two, three, four, five, six, seven, or eight N-linked glycosylation sites. In some embodiments, a Plasmodium TRAMP antigenic portion comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation. In some embodiments, a Plasmodium TRAMP antigenic portion comprises a substitution of NX[T / S] to QX[T / S], In some embodiments, a / ¥asmoa6i / fl)TRAMP antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0036] In some embodiments, a PiasmodmmTRMAP antigenic portion comprises an asparagine at position 149, position 195, position 202, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, a Plasmodium TRAMP antigenic portion comprises a glutamine at position 149, position 195, position 202, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, a Plasmodium TRAMP antigenic portion comprises a glutamine at position 149, position 195, and position 202, as numbered according to SEQ ID NO: 4. In some embodiments, a Plasmodium TRAMP antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 181.

[0037] In some embodiments, a Plasmodium TRAMP antigenic portion comprises an asparagine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, position 305, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, a Plasmodium TRAMP antigenic portion comprises a glutamine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, position 305, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, a Plasmodium TRAMP antigenic portion comprises a glutamine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, and position 305, as numbered according to SEQ ID NO: 4. In some embodiments, a Plasmodium TRAMP antigenic portion comprises or consists of an amino acid sequence according to SEQ ID NO: 180.

[0038] In some embodiments, a Plasmodium TRAMP antigenic portion comprises a PMX deavage site. In some embodiments, a PMX deavage site comprises or consists of an amino add sequence of HFLQ. In some embodiments, a Plasmodium TRAMP antigenic portion comprises a SUB2 cleavage site. In some embodiments, a SUB2 deavage site comprises or consists of an amino add sequence according to SEQ ID NO: 193.

[0039] In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise a Ptasmodum CSS polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex antigens comprise an antigenic portion of Plasmodium CSS.

[0040] In some embodiments, a Plasmodium CSS antigenic portion comprises one or more cysteine to serine mutations. In some embodiments, a Ptasmodum CSS antigenic portion comprises a C30S mutation, a C80S mutation, a C276S mutation, or a combination thereof. In some embodiments, a Plasmodium CSS antigenic portion comprises a serine at position 30 and position 80, as numbered according to SEQ ID NO: 5 or 214.

[0041] In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 194. In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 194. In some embodiments, a Plasmodium CSS antigenic portion comprises a serine at position 30 and position 276, as numbered according to SEQ ID NO: 5 or 214.

[0042] In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 195. In someembodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino acid sequence according to SEQ ID NO: 195.

[0043] In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino acid sequence according to SEQ ID NO: 182.

[0044] In some embodiments, a Plasmodium CSS antigenic portion comprises one, two, three, four, five, or six N-inked glycosylation sites. In some embodiments, a Plasmodium CSS antigenic portion comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, a Plasmodium CSS antigenic portion comprises a substitution of NX[T / S] to QX[T / S], In some embodiments, a Plasmodium CSS antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0045] In some embodiments, a Plasmodium CSS antigenic portion comprises an asparagine at position 74, position 88, or a combination thereof, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, a Plasmodium CSS antigenic portion comprises a glutamine at position 74, position 88, or a combination thereof, as numbered according to SEQ ID NO: 214.

[0046] In some embodiments, a Plasmodium CSS antigenic portion comprises a glutamine at position 74 and position 88, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 184.

[0047] In some embodiments, a Plasmodium CSS antigenic portion comprises an asparagine at position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 195. In some embodiments, a Plasmodium CSS antigenic portion comprises a glutamine at position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 195. In some embodiments, a Plasmodium CSS antigenic portion comprises a glutamine at position 192, position 234, position 261, and position 283, as numbered according to SEQ ID NO: 195. In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 185.

[0048] In some embodiments, a Plasmodium CSS antigenic portion comprises an asparagine at position 74, position 88, position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS antigenic portion comprises a glutamine at position 74, position 88, position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS antigenic portion comprises a glutamine at position 74, position 88, position 192, position 234, position 261, and position 283, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS antigenic portion comprises or consists of an amino add sequence according to SEQ ID NO: 183.

[0049] In some embodiments, a polypeptide comprises two or more Piasmodum Rh5 invasion complex polypeptides or antigenic portions thereof. In some embodiments, Rh5 invasion complex polypeptides or antigenic portions thereof comprise two selected from (I) one or more Plasmodium Rh5 polypeptides or antigenic portions thereof, (ii) one or more Plasmodium C'fRPk polypeptides or antigenic portions thereof, (iii) one or more Plasmodium Ripr polypeptides or antigenic portions thereof, (iv) one or more Plasmodium Pl 13 polypeptides or antigenic portionsthereof, (v) one or more Plasmodium TRAMP polypeptides or antigenic portions thereof, and (vi) one or more Plasmodium CSS polypeptides or antigenic portions thereof.

[0050] In some embodiments, a polypeptide comprises one or more Plasmodium Rh5 antigenic portions and further comprises: (i) one or more Plasmodium CyRPA polypeptides or antigenic portions thereof, (ii) one or more Plasmodium Ripr polypeptides or antigenic portions thereof, (iii) one or more Plasmodium P113 polypeptides or antigenic portions thereof, (iv) one or more Ptis / nodt / m TRAMP polypeptides or antigenic portions thereof, or (v) one or more Plasmodium CSS polypeptides or antigenic portions thereof.

[0051] In some embodiments, a polypeptide comprises one or more Plasmodium Rh5 antigenic portions, wherein the polypeptide comprises: (i) one or more Plasmodium Rh5 polypeptides or antigenic portions thereof and one or more Plasmodium CyRPA polypeptides or antigenic portions thereof; (il) one or more Plasmodium Rh5 polypeptides or antigenic portions thereof and one or more Plasmodium Pl 13 polypeptides or antigenic portions thereof; (iii) one or more Plasmodium Rh5 polypeptides or antigenic portions thereof and one or more a Plasmodium Ripr polypeptides or antigenic portions thereof; (hr) one or more Plasmodium Rh5 polypeptides or antigenic portions thereof and one or more a Plasmodium TRAMP polypeptides or antigenic portions thereof; or (v) one or more Plasmodium Rh5 polypeptides or antigenic portions thereof and one or more a Plasmodium CSS polypeptides or antigenic portions thereof.

[0052] In some embodiments, a polypeptide comprises a secretory signal. In some embodiments, a secretory slgial is located at the N-terminus of the polypeptide.

[0053] In some embodiments, a secretory signal is a heterologous secretory signal. In some embodiments, a heterologous secretory signal comprises or consists of a viral secretory signal. In some embodiments, a viral secretory signal comprises or consists of an HSV secretory signal. In some embodiments, an HSV secretory signal comprises or consists of an HSV-1 or HSV-2 secretory signal. In some embodiments, an HSV secretory signal comprises or consists of an HSV glycoprotein D (gD) secretory signal. In some embodiments, an HSV gD secretory signal consists of an amino add sequence according to SEQ ID NO: 42.

[0054] In some embodiments, a secretory signal comprises or consists of a Plasmodium seaetarf signal. In some embodiments, a secretory signal comprises or consists of a Plasmodium CyRPA secretory signal. In some embodiments, a secretory signal comprises or consists of a Plasmodium Ripr secretory signal. In some embodiments, a secretory signal comprises or consists of a Plasmodium CSS secretory signal. In some embodiments, a secretory signal comprises or consists of an amino add sequence according to SEQ ID NOs: 186, 187, 188.

[0055] In some embodiments, a polypeptide comprises a transmembrane region. In some embodiments, a transmembrane region comprises a heterologous transmembrane region.

[0056] In some embodiments, a transmembrane region comprises or consists of a Plasmodium transmembrane region. In some embodiments, a transmembrane region comprises or consists of a P113 Plasmodium transmembrane region. In some embodiments, a transmembrane region comprises or consists of a TRAMP Plasmodium transmembrane region.

[0057] In some embodiments, a heterologous transmembrane region comprises or consists of a viral transmembrane region. In some embodiments, a heterologous transmembrane region comprises or consists of an HSV transmembrane region. In some embodiments, an HSV transmembrane region comprises or consists of an HSV- 1 or HSV-2 transmembrane region. In some embodiments, an HSV transmembrane region comprises or consists ofan HSV gD transmembrane region. In some embodiments, an HSV gD transmembrane region consists of an amino add sequence according to SEQ ID NO: 75.

[0058] In some embodiments, a polypeptide does not comprise a transmembrane region.

[0059] In some embodiments, a polypeptide comprises a multimerization domain. In some embodiments, a multimerization domain is a trimerization domain. In some embodiments, a trimerization domain is a C -terminal domain of T4 fibritin (e.g., foldon domain). In some embodiments, a foldon domain comprises or consists of an amino acid sequence according to SEQ ID NO: 78.

[0060] In some embodiments, a polypeptide comprises a self-assembling nanoparticle domain. In some embodiments, a self-assembling nanopartide domain is a ferritin domain. In some embodiments, a ferritin domain is from H. pylori. In some embodiments, a ferritin domain comprises or consists of a sequence according to SEQ ID NO. 88.

[0061] In some embodiments, a polypeptide comprises one or more linkers. In some embodiments, a polypeptide comprises one or more glydne-serine linkers. In some embodiments, one or more linkers comprise or consist of an amino add sequence according to SEQ ID NO: 80. In some embodiments, one or more linkers comprise or consist of an amino add sequence according to SEQ ID NO: 83. In some embodiments, one or more linkers comprise or consist of an amino acid sequence according to SEQ ID NO: 84. In some embodiments, one or more linkers comprise or consist of an amino add sequence according to SEQ ID NO: 86. In some embodiments, one or more linkers comprise or consist of an amino acid sequence according to SEQ ID NO: 137. In some embodiments, one or more linkers comprise or consist of an amino add sequence according to SEQ ID NO: 138.

[0062] In some embodiments, a polypeptide comprises a linker after an amino add sequence of the one or more Plasmodium Rh5 Invasion complex polypeptides or antigenic portions thereof.

[0063] In some embodiments, Plasmodium Is Plasmodium faidparum. In some embodiments, Plasmodium falciparum is Plasmodium faidparum isolate 3D7.

[0064] In some embodiments, one or more Plasmodium Rh5 Invasion complex polypeptides or antigenic portions thereof are one or more P. faidparum Rh5 invasion complex polypeptides or antigenic portions thereof. In some embodiments, one or more Plasmodium Rh5 polypeptides or antigenic portions thereof are one or more P. falciparum Rh5 antigenic portions. In some embodiments, one or more Plasmodium Rh5 Invasion complex polypeptides or antigenic portions thereof are a P. falciparum CyRPA polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof are a P. faidparum Pl 13 polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof are a P. falciparum Ripr polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof are a P. fakiparum TRAMP polypeptide or antigenic portion thereof. In some embodiments, one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof are a P. fakiparum CSS polypeptide or antigenic portion thereof.

[0065] Provide herein is a polyribonucleotide encoding a polypeptide, wherein the polypeptide comprises a secretory signal, and two Plasmodium Rh5 ordered domains.

[0066] In some embodiments, a polypeptide comprises (i) a secretory signal, (II) two Plasmodium Rh5 ordered domains, (iH) a linker, and (iv) a multimerization domain. In some embodiments, a polypeptide comprises (I) a secretory signal, (II) two Plasmodium Rh5 ordered domains, (ill) a linker, and (iv) a transmembrane region. In someembodiments, a polypeptide comprises (i) a secretory signal, (ii) two Plasmodium Rh5 ordered domains, (iii) a linker, and (iv) a self-assembling nanoparticle domain.

[0067] In some embodiments, a secretory signal is a viral secretory signal. In some embodiments, a secretory skyial is an HSV glycoprotein D (gD) secretory signal, optionally wherein the HSV gD secretory signal consists of an amino acid sequence according to SEQ ID NO: 42.

[0068] In some embodiments, a polypeptide does not comprise a Plasmodium Rh5 disordered domain. In some embodiments, two Plasmodium Rh5 ordered domains are directly adjacent.

[0069] In some embodiments, a polypeptide comprises a C203Y substitution, as numbered according to SEQID NO: 1.

[0070] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 94. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 94.

[0071] In some embodiments, a linker comprises or consists of a glydne-serine linker. In some embodiments, a linker comprises or consists of an amino acid sequence according to SEQ ID NO: 86.

[0072] In some embodiments, a multimerization domain Is a C-terminal domain of T4 fibrttin (e.g., fokion domain). In some embodiments, a foldon domain comprises or consists of an amino acid sequence according to SEQ ID NO: 78.

[0073] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 90. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 90.

[0074] In some embodiments, a transmembrane region is a heterologous transmembrane region. In some embodiments, a transmembrane region is a viral transmembrane region. In some embodiments, a viral transmembrane region Is a HSV gD transmembrane region. In some embodiments, a HSV gD transmembrane region comprises or consists of an amino add sequence according to SEQ ID NO: 75.

[0075] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 92. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 92.

[0076] In some embodiments, a linker comprises or consists of a glycine-serine linker. In some embodiments, a linker comprises or consists of an amino acid sequence according to SEQ ID NO: 137.

[0077] In some embodiments, a self-assembling nanoparticle domain is a ferritin domain. In some embodiments, a ferritin domain comprises or consists of a sequence according to SEQ ID NO: 88.

[0078] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 96. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 96.

[0079] In some embodiments, Plasmodium Rh5 ordered domains comprise one or more N-linked glycosylation sites.

[0080] In some embodiments, Plasmodium Rh5 ordered domains comprise one NX[T / S] to QX[T / S] substitution, optionally wherein the substitution is a N214Q substitution, as numbered according to SEQ ID NO: 1.

[0081] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 99. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 99.

[0082] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 98. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 98.

[0083] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 101. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 101.

[0084] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 100. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 100.

[0085] In some embodiments, Plasmodium Rh5 ordered domains comprise two NX[T / S] to QX[T / S] substitutions, optionally wherein the two substitutions comprise N214Q and N297Q substitutions. In some embodiments, Plasmodium Rh5 ordered domains comprise an amino add substitution at al of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0086] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 95. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 95.

[0087] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 91. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 91.

[0088] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 93. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 93.

[0089] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 97. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 97.

[0090] Also provided herein is a polyribonucleotide encoding a polypeptide, wherein the polypeptide comprises (i) a secretory signal, (ii) a Plasmodium Rh5 N-terminal disordered domain, (iii) a Plasmodium Rh5 ordered domain, (iv) a Plasmodium Rh5 linking disordered domain, and (v) a Plasmodium Rh5 C-terminal ordered domain.

[0091] In some embodiments, a secretory signal Is a heterologous secretory signal. In some embodiments, a heterologous secretory signal is a viral secretory signal. In some embodiments, a viral secretor signal is an HSV glycoprotein D (gD) secretory signal. In some embodiments, an HSV gD secretory signal comprises or consists of an amino acid sequence according to SEQ ID NO: 42.

[0092] In some embodiments, a polypeptide comprises one or more N-linked glycosylation sites. In some embodiments, a polypeptide comprises an amino acid substitution at one or more of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation, optionally wherein the polypeptide comprises an amino add substitution at all of the N-linked glycosylation sites.

[0093] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 89. In some embodiments, a polypeptide is or comprises an amino add sequence according to SEQ ID NO: 89.

[0094] The present disdosure further provides a polyribonucleotide encoding a polypeptide, wherein the polypeptide comprises (i) a secretory signal, and (ii) a Plasmodium CyRPA polypeptide or antigenic portion thereof.

[0095] In some embodiments, a polypeptide comprises (i) a secretory signal, (ii) a Plasmodium CyRPA polypeptide or antigenic portion thereof, (Si) a linker, and (iv) a multimerization domain.

[0096] In some embodiments, a polypeptide comprises (i) a secretory signal, (ii) a Plasmodium CyRPA polypeptide or antigenic portion thereof, and (iii) a transmembrane region.

[0097] In some embodiments, a polypeptide comprises (i) a seaetory signal, (II) a Plasmodium Of'RPk polypeptide or antigenic portion thereof, (iii) a linker, and (iv) a transmembrane region.

[0098] In some embodiments, a secretory signal is a heterologous secretory signal. In some embodiments, a heterologous secretory signal is a viral secretory signal. In some embodiments, a viral secretor signal is an HSV glycoprotein D (gD) secretory signal. In some embodiments, an HSV gD secretory signal comprises or consists of an amino acid sequence according to SEQ ID NO: 42.

[0099] In some embodiments, a secretory signal is a Plasmodium seatiorf signal. In some embodiments, a Plasmodium secretory signal Is a Plasmodium CyRPA seaetory signal. In some embodiments, a Plasmodium CyRPA secretory signal comprises or consists of an amino add sequence according to SEQ ID NO: 187. In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence Identity to a sequence comprising SEQ ID NO: 133.

[0100] In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises or consists of SEQ ID NO: 169 or 133. In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises or consists of amino adds 29-362 of SEQ ID NO: 169 or 133.

[0101] In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises one or more N-linked glycosylation sites. In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises an amino acid substitution at one or more of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0102] In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises a substitution of NX[T / S] to QX[T / S] and / or a substitution of NX[T / S] to NXA. In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises an N145Q, N322Q, N338Q or a combination thereof. In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises an N145Q, N322Q, N338Q.

[0103] In some embodiments, a linker comprises a glydne-serine linker. In some embodiments, a linker comprises or consists of an amino acid sequence according to SEQ ID NO: 86. In some embodiments, a linker comprises or consists of an amino add sequence according to SEQ ID NO: 138.

[0104] In some embodiments, a multimerization domain is a C-terminal domain of T4 fibritin (foldon domain). In some embodiments, a foldon domain comprises or consists of an amino add sequence according to SEQ ID NO: 78.

[0105] In some embodiments, a transmembrane region is a heterologous transmembrane region. In some embodiments, a transmembrane region is a viral transmembrane region. In some embodiments, a viraltransmembrane region is a HSV gD transmembrane region. In some embodiments, a HSV gD transmembrane region comprises or consists of an amino acid sequence according to SEQ ID NO: 75.

[0106] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 140. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 140.

[0107] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 141. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 141.

[0108] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 142. In some embodiments, a polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 142.

[0109] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 143. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 143.

[0110] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 144. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 144.

[0111] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 198. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 198.

[0112] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 199. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 199.

[0113] Further provided is a polyribonucleotide encoring a polypeptide, wherein the polypeptide comprises (I) a secretory signal, (H) a Plasmodium P113 polypeptide or antigenic portion thereof, (ill) a linker, and (Iv) a transmembrane region. In some embodiments, a polypeptide comprises: (I) a secretory signal, (li) a Plasmodium P113 polypeptide or antigenic portion thereof, (Hi) a linker, and (iv) a transmembrane region.

[0114] In some embodiments, a secretory signal is a heterologous secretory signal. In some embodiments, a heterologous secretory signal is a viral secretory signal. In some embodiments, a viral secretor signal is an HSV glycoprotein D (gD) secretory signal. In some embodiments, an HSV gD secretory signal comprises or consists of an amino acid sequence according to SEQ ID NO: 42.

[0115] In some embodiments, a Ifriker comprises a glydne-serine linker. In some embodiments, a linker comprises or consists of an amino add sequence according to SEQ ID NO: 86.

[0116] In some embodiments, a transmembrane region is a heterologous transmembrane region. In some embodiments, a transmembrane region is a viral transmembrane region. In some embodiments, a viral transmembrane region is a HSV gD transmembrane region. In some embodiments, a HSV gD transmembrane region comprises or consists of an amino add sequence according to SEQ ID NO: 75.

[0117] In some embodiments, a Plasmodium P113 polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQID NO: 135. In some embodiments, a Plasmodium P113 polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 135.

[0118] In some embodiments, a Plasmodium P113 polypeptide or antigenic portion thereof comprises one or more N-linked glycosylation sites. In some embodiments, a Plasmodium P113 polypeptide or antigenic portion thereof comprises an amino acid substitution at one or more of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, a Plasmodium P113 polypeptide or antigenic portion thereof comprises one or more substitutions of NX[T / S] to QX[T / S] and / or substitutions of NX[T / S] to NXA.

[0119] In some embodiments, a Plasmodium P113 antigenic portion comprises an asparagine at position 207, position 268, position 317, position 360, position 661, position 694, position 779, position 876, or a combination thereof, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium P113 antigenic portion comprises a glutamine at position 207, position 268, position 317, position 360, position 661, position 694, position 779, position 876, or a combination thereof, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium P113 antigenic portion comprises a glutamine position 207, position 268, position 317, position 360, position 661, position 694, position 779, and position 876, as numbered according to SEQ ID NO: 6.

[0120] In some embodiments, a Plasmodium P113 polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 136.

[0121] Further provided Is a poiyribonudeotlde encoding a polypeptide, wherein the polypeptide comprises (I) a secretory signal, and (H) a Plasmodium Rlpr polypeptide or antigenic portion thereof.

[0122] In some embodiments, a polypeptide comprises (I) a secretory signal, (II) a Plasmodium Rlpr polypeptide or antigenic portion thereof, and (III) a transmembrane region.

[0123] In some embodiments, a polypeptide comprises (I) a secretory signal, (II) a Plasmodium Rlpr polypeptide or antigenic portion thereof, (ii) a linker, and (hr) a transmembrane region.

[0124] In some embodiments, a secretory signal Is a Plasmodium secretory signal. In some embodiments, a Plasmodium secretory signal Is a Plasmodium Rlpr secretory signal. In some embodiments, a Plasmodium Ripr secretory signal comprises or consists of an amino add sequence according to SEQ ID NO: 186.

[0125] In some embodiments, a secretory signal is a viral seaetory signal. In some embodiments, a secretory signal is an HSV glycoprotein D (gD) secretory signal. In some embodiments, a HSV gD secretory signal comprises or consists of an amino add sequence accorcfing to SEQ ID NO: 42.

[0126] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof Ripr comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 171. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 171.

[0127] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven or twelve N-linked glycosylation sites. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises an amino acid substitution at one or more N- linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0128] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises a substitution of NX[T / S] to QX[T / S]. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises an amino acid substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0129] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises an asparagine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 171. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises a glutamine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 171. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises a glutamine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, and position 1021, as numbered according to SEQ ID NO: 171. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 172.

[0130] In some embodiments, a linker comprises a glycine-serine linker. In some embodiments, a linker comprises or consists of an amino acid sequence according to SEQ ID NO: 138.

[0131] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 145. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 145.

[0132] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 147. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 147.

[0133] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 149. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 149.

[0134] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 151. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 151.

[0135] In some embodiments, a transmembrane region is a heterologous transmembrane region. In some embodiments, a heterologous transmembrane region comprises or consists of a viral transmembrane region. In some embodiments, a heterologous transmembrane region comprises or consists of an HSV transmembrane regon. In some embodiments, a HSV transmembrane region comprises or consists of an HSV gD transmembrane region. In some embodiments, a HSV gD transmembrane region comprises or consists of an amino acid sequence according to SEQ ID NO: 75.

[0136] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 146. In some embodments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 146.

[0137] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 200. In some embodments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 200.

[0138] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 148. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 148.

[0139] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 201. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 201.

[0140] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 150. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 150.

[0141] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 202. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 202.

[0142] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 152. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 152.

[0143] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 203. In some embedments, a polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 203.

[0144] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 178.

[0145] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 177. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 177.

[0146] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 176. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 176.

[0147] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 175. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 175.

[0148] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 174. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 174.

[0149] Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 190. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 190.

[0150] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino add substitution preventsglycosylation. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises a substitution of NX[T / S] to QX[T / S]. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises an amino acid substitution at all of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation.

[0151] In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises an asparagine at position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 190. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises a glutamine at position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 190. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises a glutamine at position 646, position 964, and position 1021, as numbered according to SEQ ID NO: 190. In some embodiments, a Plasmodium Ripr polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 173.

[0152] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 153. In some embodiments, a polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 153.

[0153] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 204. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 204.

[0154] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 154. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 154.

[0155] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 205. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 205.

[0156] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 155. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 155.

[0157] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 206. In some emboefiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 206.

[0158] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 156. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 156.

[0159] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 207. In some emboefiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 207.

[0160] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 157. In some emboefiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 157.

[0161] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 208. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 208.

[0162] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 158. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 158.

[0163] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 209. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 209.

[0164] Further provided Is a polyribonucleotide encoding a polypeptide, wherein the polypeptide comprises (I) a secretory signal, (H) a Plasmodium TRAMP polypeptide or antigenic portion thereof.

[0165] In some embodiments, a secretory signal is a viral secretory signal. In some embodiments, a secretory signal is an HSV glycoprotein D (gD) secretory signal. In some embodiments, a HSV gD secretory signal comprises or consists of an amino add sequence according to SEQ ID NO: 42.

[0166] In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 179. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 179.

[0167] In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises one, two, three, four, five, six, seven, or eight N-linked glycosylation sites. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises a substitution of NX[T / S] to QX[T / S]. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises an amino acid substitution at all of the N- linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0168] In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises an asparagine at position 149, position 195, position 202, or a combination thereof, as numbered according to SEQ ID NO: 179. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises a glutamine at position 149, position 195, position 202, or a combination thereof, as numbered according to SEQ ID NO: 179. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises a glutamine at position 149, position 195, and position 202, as numbered according to SEQ ID NO: 179. In some embodiments, a Pfasmodft / mTRAMP polypeptide or antigenic portion thereof comprises or consists of an amino acid sequence according to SEQ ID NO: 181.

[0169] In some embodiments, a PiasmodiumTRNAP polypeptide or antigenic portion thereof comprises an asparagine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, position 305, or a combination thereof, as numbered according to SEQ ID NO: 179. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises a glutamine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, position 305, or a combination thereof, as numbered according to SEQ ID NO: 179. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises a glutamine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, andposition 305, as numbered according to SEQ ID NO: 179. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 180.

[0170] In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises a PMX cleavage site. In some embodiments, a PMX deavage site comprises or consists of an amino add sequence of HFLQ. In some embodiments, a Plasmodium TRAMP polypeptide or antigenic portion thereof comprises a SUB2 cleavage site. In some embodiments, a SUB2 cleavage site comprises or consists of an amino acid sequence according to SEQ ID NO: 193.

[0171] In some embodiments, a linker comprises a glydne-serine linker. In some embodiments, a linker comprises or consists of an amino acid sequence according to SEQ ID NO: 138.

[0172] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 159. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 159.

[0173] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 160. In some embodiments, a polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 160.

[0174] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 161. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 161.

[0175] Futher provided is a polyribonudeotkie encoding a polypeptide, wherein the polypeptide comprises (I) a secretory signal, and (li) a Plasmodium CSS polypeptide or antigenic portion thereof.

[0176] In some embodiments, a polypeptide comprises (I) a secretory signal, (ii) a Plasmodium CSS polypeptide or antigenic portion thereof, and (ill) a transmembrane region.

[0177] In some embodiments, a polypeptide comprises (I) a secretory signal, (il) a Plasmodium CSS polypeptide or antigenic portion thereof, (Hi) a linker, and (iv) a transmembrane region.

[0178] In some embodiments, a secretory signal is a Plasmodium secretory signal. In some embodiments, a Plasmodium secretory signal Is a Plasmodium CSS secretory signal. In some embodiments, a Plasmodium CSS secretory signal comprises or consists of an amino add sequence according to SEQ ID NO: 188.

[0179] In some embodiments, a secretory signal is a viral secretory signal. In some embodiments, a secretory signal is an HSV glycoprotein D (gD) secretory signal. In some embodiments, a HSV gD secretory signal comprises or consists of an amino add sequence according to SEQ ID NO: 42.

[0180] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 182.

[0181] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises one, two, three, four, five, or six N-linked glycosylation sites. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises an amino add substitution at one or more N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a substitution of NX[T / S] to QX[T / S]. In some embodiments, a Plasmodium CSSpolypeptide or antigenic portion thereof comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation.

[0182] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises an asparagine at position 74, position 88, position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 74, position 88, position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 74, position 88, position 192, position 234, position 261, and position 283, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 183.

[0183] In some embodiments, a linker comprises a glydne-serine linker. In some embodiments, a linker comprises or consists of an amino acid sequence according to SEQ ID NO: 138.

[0184] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 162. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 162.

[0185] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 163. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 163.

[0186] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 164. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 164.

[0187] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 194. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 194.

[0188] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 195. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 195.

[0189] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 182.

[0190] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises one, two, three, four, five, or six N-linked glycosylation sites. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises an amino add substitution at one or more N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a substitution of NX[T / S] to QX[T / S]. In some embodiments, a Plasmodium CSSpolypeptide or antigenic portion thereof comprises an amino acid substitution at all of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation.

[0191] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises an asparagine at position 74, position 88, or a combination thereof, as numbered according to SEQ ID NO: 194. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 74, position 88, or a combination thereof, as numbered according to SEQ ID NO: 194. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 74 and position 88, as numbered according to SEQ ID NO: 194. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino acid sequence according to SEQ ID NO: 184.

[0192] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises an asparagine at position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 195. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 195. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 192, position 234, position 261, and position 283, as numbered according to SEQ ID NO: 195. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino add sequence according to SEQ ID NO: 185.

[0193] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises an asparagine at position 74, position 88, position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 74, position 88, position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a glutamine at position 74, position 88, position 192, position 234, position 261, and position 283, as numbered according to SEQ ID NO: 182. In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises or consists of an amino acid sequence according to SEQ ID NO: 183.

[0194] In some embodiments, a first linker and / or second linker comprises or consists of an amino add sequence according to SEQ ID NO: 138.

[0195] In some embodiments, a transmembrane region is a heterologous transmembrane region. In some embodiments, a heterologous transmembrane region comprises or consists of a viral transmembrane region. In some embodiments, a heterologous transmembrane region comprises or consists of an HSV transmembrane region. In some embodiments, a HSV transmembrane region comprises or consists of an HSV gD transmembrane region. In some embodiments, a HSV gD transmembrane region comprises or consists of an amino add sequence accorcSng to SEQ ID NO: 75.

[0196] In some embodiments, a linker comprises a glydne-serine linker. In some embodiments, a linker comprises or consists of an amino acid sequence according to SEQ ID NO: 138.

[0197] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 165. In some embodiments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 165.

[0198] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 166. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 166.

[0199] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 167. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 167.

[0200] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 168. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 168.

[0201] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 210. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 210.

[0202] In some embodiments, a polypeptide comprises or consists of an amino acid sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 211. In some embedments, a polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 211.

[0203] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 212. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 212.

[0204] In some embodiments, a polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 213. In some embedments, a polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 213.

[0205] In some embodiments, an RNA construct comprises, In 5' to 3' order (I) a 5' UTR, (li) a polyribonucleotide described herein, (ill) a 3' UTR, and (Iv) a polyA tall sequence.

[0206] In some embodiments, an RNA construct comprises (i) a 5' UTR that comprises or consists of a modified human alpha-globin 5 -UTR; and (ii) a 3' UTR that comprises or consists of a first sequence from the amino terminal enhancer of split (AES) messenger.

[0207] In some embodiments, an RNA construct comprises a 5' UTR. In some embodiments, a 5' UTR comprises or consists of a modified human alpha-globin 5 -UTR. In some embodiments, a 5' UTR consists of a ribonudeic add sequence according to SEQ ID NO: 111.

[0208] In some embodiments, an RNA construct comprises a 3' UTR. In some embodiments, a 3' UTR that comprises or consists of a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA. In some embodiments, a 3’ UTR consists of a ribonudeic add sequence according to SEQ ID NO: 117.

[0209] In some embodiments, an RNA construct comprises a polyA tail sequence. In some embodiments, a polyA tail sequence is a split polyA tail sequence. In some embodiments, a split polyA tail sequence consists of a ribonudeic add sequence according to SEQ ID NO: 114.

[0210] In some embodiments, an RNA construct comprises a 5* cap.

[0211] In some embodiments, an RNA construct comprises a cap proximal sequence comprising positions +1,+2, +3, +4, and +5 of the polyribonudeotide.

[0212] In some embodiments, a 5’ cap comprises or consists of m7(3'OMeG)(5’)ppp(5')(2,OMeAi)pGz, wherein Ai is position +1 of the polyribonucleotide, and Gz is position +2 of the polyribonucleotide.

[0213] In some embodiments, a cap proximal sequence comprises Ai and Gz of the Capl structure, and a sequence comprising: A3A4U5 (SEQ ID NO: 138) at positions +3, +4 and +5 respectively of the polyribonucleotide.

[0214] In some embodiments, a polyribonucleotide provided herein indudes modified uridines in place of all uridines. In some embodiments, modified uridines are each Nl-methyl-pseudouridine.

[0215] The present disdosure also provides compositions. In some embodiments, a composition comprises one or more polyribonucleotides provided herein. In some embodiments, a composition comprises one or more RNA constructs provided herein.

[0216] In some embodiments, a composition comprises (i) one or more polyribonucleotides and (II) lipid nanopartides, polyptexes (PLX), lipidated polyptexes (LPLX), or liposomes. In some embodiments, the one or more polyribonudeotldes are fully or partially encapsulated within the lipid nanopartides, polyplexes (PLX), lipidated polyplexes (LPLX), or liposomes.

[0217] In some embodiments, a composition comprises (i) one or more polyribonudeotldes and (li) lipid nanopartides. In some embodiments, the one or more polyribonucleotides are fully or partially encapsulated within the lipid nanoparticles.

[0218] The present disdosure provides pharmaceutical compositions. In some embodiments, a pharmaceutical composition comprises (I) one or more polyribonucleotides as described herein, one or more RNA constructs as described herein, or a composition as described herein, and (II) at least one pharmaceutically acceptable exdpient

[0219] In some embodiments, a pharmaceutical comprises a cryoprotectant. In some embodiments, a cryoprotectant Is sucrose.

[0220] In some embodiments, a pharmaceutical comprises an aqueous buffered solution, optionally wherein the aqueous buffered solution comprises one or more of Tris base, Tris HCI, NaCI, KCI, NazHPCU, and KHzPO«.

[0221] The present disdosure provides, among other things, a combination comprising (i) a first pharmaceutical composition comprising a first polyribonudeotide, wherein the first polyribonucleotide encodes a first polypeptide, and the first polypeptide comprises one or more Plasmodium Rh5 polypeptides or antigenic portions thereof, and (ii) a second pharmaceutical composition comprising a second polyribonudeotide, wherein the second polyribonucleotide encodes a second polypeptide, the second polypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides selected from one or more CyRPA polypeptides or antigenic portions thereof, one or more Ripr polypeptides or antigenic portions thereof, one or more P113 polypeptides or antigenic portions thereof, one or more TRAMP polypeptides or antigenic portions thereof, one or more CSS polypeptides or antigenic portions thereof, or a combination thereof.

[0222] In some embodiments, a second polypeptide comprises one or more one or more CyRPA polypeptides or antigenic portions thereof. In some embodiments, a second polypeptide comprises one or more one or more Pl 13 polypeptides or antigenic portions thereof. In some embodiments, a second polypeptide comprises one or more one or more Ripr polypeptides or antigenic portions thereof. In some embodiments, a second polypeptide comprises one or more one or more TRAMP polypeptides or antigenic portions thereof. In some embodiments, a second polypeptide comprises one or more one or more CSS polypeptides or antigenic portions thereof.

[0223] The present disclosure also provides a combination comprising (i) a first pharmaceutical composition comprising a first polyribonudeotide, wherein the first polyribonudeotide encodes a first polypeptide, and the firstpdypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof; and (ii) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide encodes a second polypeptide, the second polypeptide comprises one or more PiasmodiumT cell antigens.

[0224] Further, the present disclosure provides a combination comprising: (i) a first pharmaceutical composition comprising a first polyribonucleotide encoding a first polypeptide, and the first polypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof; and (ii) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide encodes a second polypeptide, the second polypeptide comprises one or more Plasmodium CSV polypeptides or antigenic portions thereof.

[0225] Among other things, a method comprising administering a polyribonucleotide as described herein to a subject. The present disclosure also provides a method comprising administering an RNA construct described herein to a subject. The present disclosure further provides a method comprising administering a composition described herein to a subject. Additionally, a method comprising administering one or more doses of the pharmaceutical composition described herein to a subject.

[0226] In some embodiments, a pharmaceutical composition as provided herein Is for use in the treatment of a malaria Infection comprising administering one or more doses of the pharmaceutical composition to a subject.

[0227] In some embodiments, a pharmaceutical composition as provided herein Is for use in the prevention of a malaria Infection comprising administering one or more doses of the pharmaceutical composition to a subject

[0228] In some embodiments, administering two or more doses of the pharmaceutical conrposltlon to a subject. In some embodiments, administering three or more doses of the pharmaceutical composition to a subject

[0229] In some embodiments, a method provided herein comprises administering a combination as described herein to a subject.

[0230] In some embodiments, a first pharmaceutical composition and the second pharmaceutical composition are administered on the same day. In some embodiments, a first pharmaceutical composition and the second pharmaceutical composition are administered on different days. In some embodiments, a pharmaceutical composition and the second pharmaceutical composition are administered to the subject at (Afferent locations on the subjects body.

[0231] In some embodiments, a method is a method of treating a malaria infection.

[0232] In some embodiments, a method is a method of preventing a malaria infection.

[0233] In some embodiments, a subject has or is at risk of developing a malaria infection.

[0234] In some embodiments, a subject is a human.

[0235] In some embodiments, administration induces an anti-malaria immune response in the subject. In some embodiments, an anti-malaria immune response in the subject comprises an adaptive immune response. In some embodiments, an anti-malaria immune response in the subject comprises a T-cell response. In some embodiments, a T-cell response is or comprises a CD4+ T cell response. In some embodiments, a T-cell response is or comprises a CD6+ T cell response. In some embodiments, an anti-malaria immune system response comprises a B-cell response. In some embodiments, an anti-malaria immune system response comprises the production of antibodies directed against the one or more Plasmodium antigens.

[0236] The present disdosure provides a use of the pharmaceutical composition as described herein in the treatment of a malaria infection.

[0237] The present disdosure provides a use of the pharmaceutical composition as described herein in the prevention of a malaria infection.

[0238] The present disdosure provides a use of the pharmaceutical composition as described herein in inducing an anti-malaria immune response in a subject.

[0239] Additionally, the present disdosure provides a polypeptide encoded by a polyribonucleotide described herein or an RNA construct described herein.

[0240] The present disclosure also provides a host cell comprising a polyribonucleotide described herein or an RNA construct described herein. The present disclosure further provides a host cell comprises a polypeptide described herein.BRIEF DESCRIPTION OF THE DRAWING

[0241] FIG. 1 provides an annotated polypeptide corresponding to the P. falciparum Rh5 sequence set out in SEQ ID NO: 1. Certain sequence features are annotated, including secretory signal sequence (red bold corresponds to the signal peptide as described by Baum et al. 2009, the additional 2 red residues are included in the signal peptide description by Wright et al. 2014), glycosylation sites (NXS / T, blue and bold, lower prediction scores in blue only, the motif in brackets is proximal to the basigin binding site), Rh5 PMX cleavage site (black bold), the 3D7 reference sequence has a cysteine at position 203 (red) which is often a tyrosine in naturaNy circulating parasite isolates, paired cysteines are color coded accordingly, and underlined regions are ordered and form the alpha helical composition of the kite structure of the protein, which is associated with basigin binding.

[0242] FIG. 2, parts (A) through (M), includes schematics of exemplary polypeptides encoded by poiyribonudeotkles provided herein. All amino add (aa) references induded refer to the P. falciparum Rh5 sequence set out in SEQ ID NO: 1. (A) includes a schematic of an exemplary polypeptide, RNA Construct 1, encoded by a polyribonudeotlde described herein. RNA Construct 1 comprises an KSV glycoprotein D (gD) secretory signal (e.g., SEQ ID NO: 42), an Rh5 N-terminal "N" disordered region (aa 25-139), an Rh5 ordered region (aa 140-247), an Rh5 linking "L" disordered region (aa 248-296), and an Rh5 ordered region (aa 297-526). Four glycosylation sites at positions 38, 284, 214, and 297 have been mutated from N-X-[T / S] to N-X-A (where X is not proline). (B) indudes a schematic of an exemplary polypeptide, RNA Construct 2, encoded by a polyribonucleotide described herein. RNA Construct 2 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation, an Rh5 ordered region (aa 297-526), a glydne-serine linker (e.g., SEQ ID NO: 86), and a foldon domain. (C) indudes a schematic of an exemplary polypeptide, RNA Construct 3, encoded by a polyribonudeotlde described herein. RNA Construct 3 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation, and an Rh5 ordered region (297-526). (D) indudes a schematic of an exemplary polypeptide, RNA Construct 4, encoded by a polyribonucleotide described herein. RNA Construct 4 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation, an Rh5 ordered region (297-526), a glydne-serine linker (e.g., SEQ ID NO: 137), and a ferritin domain. (E) Indudes a schematic of an exemplary polypeptide, RNA Construct 5, encoded by a polyribonudeotlde described herein. Membrane RNA Construct 5 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation, an Rh5 ordered region (297-526), aglydne-serine linker (e.g., SEQ ID NO: 86), and an HSV gD transmembrane region (e.g., SEQ ID NO: 75). (F) indudes a schematic of an exemplary polypeptide, RNA Construct 6, encoded by a polyribonucleotide described herein. RNA Construct 6 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297-526) comprising an N297Q mutation, a glycine-serine linker (e.g., SEQ ID NO: 86), and a foldon domain. (G) indudes a schematic of an exemplary polypeptide, RNA Construct 7, encoded by a polyribonucleotide described herein. RNA Construct 7 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297-526) comprising an N297Q mutation. (H) indudes a schematic of an exemplary polypeptide, RNA Construct 8, encoded by a polyribonucleotide described herein. Self assembling RNA Construct 8 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297- 526) comprising an N297Q mutation, a glydne-serine linker (e.g., SEQ ID NO: 137), and a ferritin domain. (I) Indudes a schematic of an exemplary polypeptide, RNA Construct 9, encoded by a polyribonucleotide described herein. RNA Construct 9 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297-526) comprising an N297Q mutation, a glydne-serine linker (e.g., SEQ ID NO: 86), and an HSV gD transmembrane region (e.g., SEQ ID NO: 75). (J) indudes a schematic of an exemplary polypeptide, RNA Construct 10, encoded by a polyribonucleotide described herein. RNA Construct 10 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297-526), a glydne-serine linker (e.g., SEQ ID NO: 86), and a foldon domain. (K) indudes a schematic of an exemplary polypeptide, RNA Construct 11, encoded by a polyribonucleotide described herein. RNA Construct 11 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297-526). (L) Indudes a schematic of an exemplary polypeptide, RNA Construct 12, encoded by a polyribonucleotide described herein. RNA Construct 12 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297-526), a glycine-serine linker (e.g., SEQ ID NO: 137), and a ferritin domain. (M) includes a schematic of an exemplary polypeptide, RNA Construct 13, encoded by a polyribonudeotkie described herein. RNA Construct 13 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), an Rh5 ordered region (aa 140-247) comprising a C203Y mutation and an N214Q mutation, an Rh5 ordered region (aa 297-526), a glydne-serine linker (e.g., SEQ ID NO: 86), and an HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0243] FIG. 3 provides an annotated polypeptide corresponding to the P. falciparum CyRPA sequence set out In SEQ ID NO: 3. Certain sequence features are annotated, Indudlng secretory signal sequence (red) and glycosylation sites (NXS / T, blue).

[0244] FIG. 4, parts (A) through (F), includes schematics of exemplary polypeptide encoded by polyribonudeotides provided herein. All amino add (aa) references induded refer to the P. falciparum C / RPk sequence set out in SEQ ID NO: 3. (A) includes a schematic of an exemplary polypeptide, RNA Construct 14, encoded by a polyribonudeotkie described herein. RNA Construct 14 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of CyRPA (aa 30-362), a glydne-serine linker (e.g., SEQ ID NO: 86), and a foldon tag. (B) indudes a schematic of an exemplary polypeptide, RNA Construct 15, encoded by a polyribonucleotide described herein. RNA Construct IScomprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), and a portion of CyRPA (aa30-362). (C) includes a schematic of an exemplary polypeptide, RNA Construct 16, encoded by a polyribonucleotide described herein. RNA Construct 16 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of CyRPA (aa 30-362), a glydne-serine linker (e.g., SEQ ID NO: 86), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (D) includes a schematic of an exemplary polypeptide, RNA Construct 17, encoded by a polyribonucleotide described herein. RNA Construct 17 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of CyRPA (aa 30-362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino acid positions 145, 332, and 338, as numbered according to SEQ ID NO: 3), a glycine-serine linker (e.g., SEQ ID NO: 86), and a foidon tag. (E) includes a schematic of an exemplary polypeptide, RNA Construct 18, encoded by a polyribonucleotide described herein. RNA Construct 18 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), and a portion of CyRPA (aa 30-362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X Is not proline) at three glycosylation sites. (F) includes a schematic of an exemplary polypeptide, RNA Construct 19, encoded by a polyribonudeotlde described herein. RNA Construct 19 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of CyRPA (aa 30-362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites, a glycine-serine linker (e.g., SEQ ID NO: 86), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0245] FIG. 5, parts (A) through (G), Includes schematics of exemplary polypeptide encoded by polyribonucleotides provided herein. All amino add (aa) references Included refer to the P. fatoparum CyRPA sequence set out h SEQ ID NO: 3. Polypeptides may optionally Include one or more linkers between various regions and / or domains. (A) Indudes a schematic of an exemplary polypeptide, RNA Construct 22, encoded by a polyribonudeotlde described herein. RNA Construct 22 comprises CyRPA secretory signal (SEQ ID NO: 187) and a portion of CyRPA (aa 29-362). (B) indudes a schematic of an exemplary polypeptide, RNA Construct 23, encoded by a polyribonucleotide described herein. RNA Construct 23 comprises a CyRPA secretory signal (SEQ 10 NO: 187) and a portion of CyRPA (aa 29-362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino add positions 145, 332, and 338, as numbered according to SEQ ID NO: 3). (C) indudes a schematic of an exemplary polypeptide, RNA Construct 24, encoded by a polyribonudeotlde described herein. RNA Construct 24 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42) and a portion of CyRPA (aa 29- 362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino add positions 145, 332, and 338, as numbered according to SEQ ID NO: 3). (D) includes a schematic of an exemplary polypeptide, RNA Construct 25, encoded by a polyribonucleotide described herein. RNA Construct 25 comprises a full-length CyRPA (aa 1-362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino add positions 145, 332, and 338, as numbered according to SEQ ID NO: 3) and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (E) Indudes a schematic of an exemplary polypeptide, RNA Construct 26, encoded by a polyribonucleotide described herein. RNA Construct 26 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CyRPA (aa 29-362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino add positions 145, 332, and 338, as numbered according to SEQ ID NO: 3) and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (F) includes a schematic of an exemplary polypeptide, RNA Construct 51, encoded by a polyribonucleotide described herein. RNA Construct 51 comprises a full-length CyRPA (aa 1-362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino add positions 145, 332, and 338, as numbered according to SEQ ID NO: 3), a glycine-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (G)indudes a schematic of an exemplary polypeptide, RNA Construct 52, encoded by a polyribonudeotlde described herein. RNA Construct 52 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CyRPA (aa 29- 362) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino add positions 145, 332, and 338, as numbered according to SEQ ID NO: 3), a glycine-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0246] FIG. 6, parts (A) and (8) includes schematics of exemplary polypeptide encoded by pdyribonudeotides provided herein. All amino add (aa) references included refer to the P. falciparum P113 sequence set out in SEQ ID NO: 6. (A) includes a schematic of an exemplary polypeptide, RNA Construct 20, encoded by a polyribonudeotlde described herein. RNA Construct 20 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of P113 (aa 23-939), a glydne-serine linker (e.g., SEQ ID NO: 86), and an HSV gD transmembrane region (e.g., SEQ ID NO: 75). (B) includes a schematic of an exemplary polypeptide, RNA Construct 21, encoded by a polyribonudeotlde described herein. RNA Construct 21 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of P113 (aa 23-939) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at eight glycosylation sites (e.g., at amino add positions 207, 268, 317, 360, 661, 697, 779, 876, 938, as numbered according to SEQ ID NO: 6), a glycine-serine linker (e.g., SEQ ID NO: 86), and an HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0247] FIG. 7 provides an annotated polypeptide corresponding to the A falciparum Ripr sequence set out In SEQ ID NO: 2. Certain sequence features are annotated, including secretory signal sequence (red), glycosylation sites (NXS / T, blue, stronger predictions in bold), Ripr PMX cleavage site (green), epidermal growth factor domains as described by Chen et al. 2011 are underlined, and the domain In bold Is EGF 7 which has been associated with driving the strongest growth Inhibitory responses (Healer 2019, Nagaoka 2020).

[0248] FIG. 8, parts (A) through (L) Includes schematics of exemplary polypeptides encoded by pdyribonudeotides provided herein. All amino add (aa) references included refer to the P. falciparum Ripr sequences set out in SEQ ID NO: 2. Polypeptides may optionally Include one or more linkers between various regions and / or domains. (A) includes a schematic of an exemplary polypeptide, RNA Construct 27, encoded by a polyribonudeotlde described herein. RNA Construct 27 comprises a Ripr secretory signal (SEQ ID NO: 186) and a portion of Ripr (aa 20- 1086), a glycine-serine linker (e.g., SEQ ID NO: 138). (B) includes a schematic of an exemplary polypeptide, RNA Construct 28, encoded by a polyribonudeotlde described herein. RNA Construct 28 comprises a Ripr secretory signal (SEQ ID NO: 186), a portion of Ripr (aa 20-1086) and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (C) indudes a schematic of an exemplary polypeptide, RNA Construct 29, encoded by a polyribonudeotlde described herein. RNA Construct 29 comprises a Ripr secretory signal (SEQ ID NO: 186) and a portion of Ripr (aa 20-1086) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X Is not proline) at twelve glycosylation sites (e.g., at amino add positions 103, 144, 228, 303, 334, 480, 498, 506, 526, 646, 964, and 1021 as numbered according to SEQ ID NO: 2). (D) indudes a schematic of an exemplary polypeptide, RNA Construct 30, encoded by a polyribonucleotide described herein. RNA Construct 30 comprises a Ripr secretory signal (SEQ ID NO: 186), a portion of Ripr (aa 20- 1086) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at twelve glycosylation sites (e.g., at amino acid positions 103, 144, 228, 303, 334, 480, 498, 506, 526, 646, 964, and 1021 as numbered according to SEQ ID NO: 2), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (E) indudes a schematic of an exemplary polypeptide, RNA Construct 31, encoded by a polyribonucleotide described herein. RNA Construct 31 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42) and a portion of Ripr (aa 20-1086). (F) indudes aschematic of an exemplary polypeptide, RNA Construct 32, encoded by a polyribonucleotide described herein. RNA Construct 32 comprises a an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of Ripr (aa 20-1086), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (G) includes a schematic of an exemplary polypeptide, RNA Construct 33, encoded by a polyribonucleotide described herein. RNA Construct 33 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42) and a portion of Ripr (aa 20-1086) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at twelve glycosylation sites (e.g., at amino acid positions 103, 144, 228, 303, 334, 480, 498, 506, 526, 646, 964, and 1021 as numbered according to SEQ ID NO: 2). (H) includes a schematic of an exemplary polypeptide, RNA Construct 34, encoded by a polyribonucleotide described herein. RNA Construct 34 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 20-1086) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at twelve glycosylation sites (e.g., at amino add positions 103, 144, 228, 303, 334, 480, 498, 506, 526, 646, 964, and 1021 as numbered according to SEQ ID NO: 2), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (I) hdudes a schematic of an exemplary polypeptide, RNA Construct53, encoded by a polyribonucleotide described herein. RNA Construct 53 comprises a Ripr secretory signal (SEQ ID NO: 186), a portion of Ripr (aa 20-1086), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (J) indudes a schematic of an exemplary polypeptide, RNA Construct54, encoded by a polyribonucleotide described herein. RNA Construct 54 comprises a Ripr secretory signal (SEQ ID NO: 186), a portion of Ripr (aa 20-1086) comprising N-X-(T / S] to Q-X-[T / S] mutations (where X Is not proline) at twelve glycosylation sites (e.g., at amino acid positions 103, 144, 228, 303, 334, 480, 498, 506, 526, 646, 964, and 1021 as numbered according to SEQ JD NO: 2), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (K) Includes a schematic of an exemplary polypeptide, RNA Construct55, encoded by a polyribonudeotide described herein. RNA Construct 55 comprises a an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of Ripr (aa 20-1086), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (L) Includes a schematic of an exemplary polypeptide, RNA Construct56, encoded by a polyribonudeotide described herein. RNA Construct 56 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 20-1086) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at twelve glycosylation sites (e.g., at amino add positions 103, 144, 228, 303, 334, 480, 498, 506, 526, 646, 964, and 1021 as numbered according to SEQ ID NO: 2), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0249] FIG. 9, parts (A) through (L) includes schematics of exemplary polypeptides encoded by pdyribonudeotides provided herein. All amino add (aa) references included refer to the P. falciparum Ripr sequences set out in SEQ ID NO: 2. Polypeptides may optionally indude one or more linkers between various regions and / or domains. (A) includes a schematic of an exemplary polypeptide, RNA Construct 35, encoded by a polyribonudeotide described herein. RNA Construct 35 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 560-1086) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at twelve glycosylation sites (e.g., at amino add positions 646, 964, and 1021 as numbered according to SEQ ID NO: 2), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (B) indudes a schematic of an exemplary polypeptide, RNA Construct 36, encoded by a polyribonudeotide described herein. RNA Construct 36 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 720-934), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (C) indudes a schematic of an exemplary polypeptide, RNA Construct 37, encoded by a polyribonudeotide described herein. RNA Construct 37 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 769-900) and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (D) indudes a schematic of an exemplary polypeptide, RNA Construct 38, encoded by a polyribonucleotide described herein. Membrane Ripr comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 769-856) and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (E) indudes a schematic of an exemplary polypeptide, Membrane Ripr, encoded by a polyribonudeotide described herein. RNA Construct 38 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 817-900), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (F) includes a schematic of an exemplary polypeptide, RNA Construct 40, encoded by a polyribonudeotide described herein. RNA Construct 40 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 817-856), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (G) indudes a schematic of an exemplary polypeptide, RNA Construct 57, encoded by a pdyribonudeotide described herein. RNA Construct 57 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 560-1086) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at twelve glycosylation sites (e.g., at amino acid positions 646, 964, and 1021 as numbered according to SEQ ID NO: 2), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (H) includes a schematic of an exemplary polypeptide, RNA Construct 58, encoded by a pdyribonudeotide described herein. RNA Construct 58 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 720-934), a glydne-serine inker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (I) indudes a schematic of an exemplary polypeptide, RNA Construct 59, encoded by a polyribonucleotide described herein. RNA Construct 59 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 769-900), a glydne-serine inker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (J) Indudes a schematic of an exemplary polypeptide, RNA Construct 60, encoded by a pdyribonudeotide described herein. RNA Construct 60 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 769-856), a glydne-serine inker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (K) indudes a schematic of an exemplary polypeptide, RNA Construct 61, encoded by a pdyribonudeotide described herein. RNA Construct 61 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 817-900), a glydne-serine inker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (L) Includes a schematic of an exemplary pdypeptlde, RNA Construct 62, encoded by a polyribonucleotide described herein. RNA Construct 62 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a portion of Ripr (aa 817-856), a glydne-serine inker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0250] FIG. 10 provides an annotated polypeptide corresponding to the P. fataparum'VV.NAV sequence set out in SEQ ID NO: 4. Certain sequence features are annotated, induding secretory signal sequence (red), glycosylation sites (NXS / T, blue), TRAMP deavage site (bold), and SUB2 deavage site (green).

[0251] FIG. 11, parts (A) through (C) indudes schematics of exemplary polypeptides encoded by pdyribonudeotides provided herein. All amino add (aa) references included refer to the P. faldparum'ttMW sequences set out in SEQ ID NO: 4. Polypeptides may optionally indude one or more linkers between various regions and / or domains. (A) indudes a schematic of an exemplary polypeptide, RNA Construct 41, encoded by a polyribonudeotide described herein. RNA Construct 41 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42) and a portion of TRAMP (aa 42-352). (B) indudes a schematic of an exemplary polypeptide, RNA Construct 42, encoded by a polyribonudeotide described herein. RNA Construct 42 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42) and a portion of TRAMP (aa 42-352) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is notproline) at eight glycosylation sites (e.g., at amino acid positions, 112, 149, 155, 170, 195, 202, 253, and 305, as numbered according to SEQ ID NO: 4). (C) includes a schematic of an exemplary polypeptide, RNA Construct 43, encoded by a polyribonucleotide described herein. RNA Construct 43 comprises an HSV gD secretory signal (SEQ ID NO:42) and a portion of TRAMP (aa 42-352) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at three glycosylation sites (e.g., at amino acid positions, 149, 195, and 202, as numbered according to SEQ ID NO: 4).

[0252] FIG. 12 provides an annotated polypeptide corresponding to the P. falciparum CSS sequence set out in SEQ ID NO: 5. Certain sequence features are annotated, including secretory signal sequence (red), glycosylation sites (NXS / T, blue), domains DI and D2 are underlined and joined by the linker region in purple.

[0253] FIG. 13, parts (A) through (K) includes schematics of exemplary polypeptides encoded by polyribonucleotides provided herein. All amino add (aa) references Included refer to the P. falciparum CSS sequences set out in SEQ ID NO: 5. Polypeptides may optionally indude one or more linkers between various regions and / or domains. (A) includes a schematic of an exemplary polypeptide, RNA Construct 44, encoded by a polyribonudeotide described herein. RNA Construct 44 comprises a CSS secretory signal (SEQ ID NO: 188) and a portion of CSS (aa 21- 290). (B) includes a schematic of an exemplary polypeptide, RNA Construct 45, encoded by a polyribonucleotide described herein. RNA Construct 45 comprises a CSS secretory signal (SEQ ID NO: 188) and a portion of CSS (aa 21- 290) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at six glycosylation sites (e.g., at amino add positions 74, 88, 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5). (C) includes a schematic of an exemplary polypeptide, RNA Construct 46, encoded by a polyribonudeotide described herein. RNA Construct 46 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42) and a portion of CSS (aa 21-290) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at six glycosylation sites (e.g., at amino acid positions 74, 88, 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5). (D) Includes a schematic of an exemplary polypeptide, RNA Construct 47, encoded by a polyribonudeotide described herein. RNA Construct 47 comprises a CSS secretory signal (SEQ ID NO: 188), a portion of CSS (aa 21-290) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at six glycosylation sites (e.g., at amino add positions 74, 88, 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (E) indudes a schematic of an exemplary polypeptide, RNA Construct 48, encoded by a polyribonucleotide described herein. RNA Construct 48 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CSS (aa 21-290) comprising N-X-[T / S] to Q- X-[T / S] mutations (where X is not proline) at six glycosylation sites (e.g., at amino add positions 74, 88, 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (F) includes a schematic of an exemplary polypeptide, RNA Construct 49, encoded by a polyribonucleotide described herein. RNA Construct 49 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CSS (aa 21-152) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X Is not proline) at two glycosylation sites (e.g., at amino add positions 74 and 88, as numbered according to SEQ ID NO: 5), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (G) includes a schematic of an exemplary polypeptide, RNA Construct 50, encoded by a polyribonudeotide described herein. RNA Construct 50 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CSS (aa 153-290) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at four glycosylation sites (e.g., at amino acid positions 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (H) indudes a schematic of an exemplary polypeptide, RNA Construct 63, encoded by a polyribonudeotide described herein. RNA Construct 63 comprises a CSS secretory signal (SEQ ID NO: 188), a portion of CSS (aa 21-290) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at sixglycosylation sites (e.g., at amino acid positions 74, 88, 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (I) includes a schematic of an exemplary polypeptide, RNA Construct 64, encoded by a polyribonudeotide described herein. RNA Construct 64 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CSS (aa 21-290) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at six glycosylation sites (e.g., at amino acid positions 74, 88, 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (J) indudes a schematic of an exemplary polypeptide, RNA Construct 65, encoded by a polyribonucleotide described herein. RNA Construct 65 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CSS (aa 21-152) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X Is not proline) at two glycosylation sites (e.g., at amino add positions 74 and 88, as numbered according to SEQ ID NO: 5), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (K) indudes a schematic of an exemplary polypeptide, RNA Construct 66, encoded by a polyribonudeotide described herein. RNA Construct 66 comprises an HSV gD secretory signal (e.g., SEQ ID NO:42), a portion of CSS (aa 153-290) comprising N-X-[T / S] to Q-X-[T / S] mutations (where X is not proline) at four glycosylation sites (e.g., at amino add positions 192, 234, 261, and 283 as numbered according to SEQ ID NO: 5), a glydne-serine linker (e.g., SEQ ID NO: 138), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0254] FIG. 14, parts (A) through (F) depicts In-vitro host cell viabllty, transfection rate, and expression of polyribonudeotide constructs encoding Plasmodium polypeptides as described herein by host cells (e.g., HEK293T cells). (A) depicts the percentage of viable host cells that are positive for presence of Intracellularly expressed protein for both transfected and non-transfected (NT) cells. (B) percentage of viable host cells that are positive for presence of surface expressed protein for both transfected and non-transfected cells. (C) depicts transfection rate of Indicated polyribonudeotide constructs as measured by percentage of total host cell population that are positive for presence of Intracellularly expressed protein. (D) depicts transfection rate of Indicated polyribonudeotide constructs as measured by percentage of total host cell population that are positive for presence of surface expressed protein. (E) depicts total Intracellular protein expression as measured by median fluorescence Intensity of the total host cell population for both transfected and non-transfected cells. (F) depicts total surface protein expression as measured by median fluorescence of the total host cell population for both transfected and non-transfected cells. Numbers depicted at x-axis indicate RNA construct number. NT stands for non-transfected.

[0255] FIG. 15, parts (A) through (D) depict transfection rate and expression of polyribonudeotide constructs encoding Plasmodium polypeptides as described herein by host cells (e.g., HEK293T cells). (A) depicts transfection rate of indicated polyribonucleotide constructs as measured by percentage of total host cell population that are positive for presence of intracellularly expressed protein. (B) depicts transfection rate of indicated polyribonucleotide constructs as measured by percentage of total host cell population that are positive for presence of surface expressed protein. (C) depicts total intracellular protein expression as measured by median fluorescence intensity of the total host cell population for both transfected and non-transfected cells. (D) depicts total surface protein expression as measured by median fluorescence of the total host cell population for both transfected and non- transfected cells. Numbers depicted at x-axis indicate RNA construct number. NT stands for non-transfected.

[0256] FIG. 16, parts (A) and (B) depict transfection rate and expression of polyribonucleotide constructs encoding Plasmodium polypeptides as described herein by HEK293T cells. (A) depicts transfection rate of indicated polyribonudeotide constructs as measured by percentage of total host cell popdation that are positive for presenceof intracellularly expressed protein. For each construct shown, cells were stained using day 35 serum at 1:1000 dilution from mice immunized twice with the same construct. Cells transfected with construct 23 were stained using serum from mice immunized with construct 23. Construct 1, which encodes RH5, was induded as a control, as ELISA and IVE data with monodonal antibodies have already confirmed immunogenidty for these constructs. Construct 1 was stained with both the monoclonal antibody 9AD4 at 1:2000 dilution and serum from mice immunized with construct 1. (B) depicts total protein expression as measured by median fluorescence intensity of the total host cell population for both non-transfected and transfected cells. For all constructs, un-transfected cells (-) were induded as a negative control, (+) indicates cells that were transfected with the matching construct before staining. Numbers depicted at x-axIs indicate RNA construct number. NT stands for non-transfected.

[0257] FIG. 17 parts (A) through (J) depict in-vitro expression of polyribonudeotlde constructs encoding Plasmodium polypeptides as described herein by host cells (e.g., HEK293T cells). In-vitro expression was measured by detecting the protein associated with cells, either intracellular or surface bound, or the protein detected in the culture medium (e.g., exported). (A) depicts total cell-associated protein expression determined with a HiBit luminescence assay for GARP constructs and (B) depicts total exported protein detected In the culture medium for GARP constructs. (C) depicts total cell-assodated protein expression determined with the HiBit luminescence assay for CyRPA constructs and (D) depicts total exported protein detected in the culture medium for CyRPA constructs. (E) depicts total cell-assodated protein expression determined with the HiBit luminescence assay for Rlpr constructs, and (F) depicts total exported protein detected In the culture medium for Rlpr constructs. (G) depicts total cell- assodated protein expression determined with the HiBit luminescence assay for CSS constructs, and (H) depicts total exported protein detected In the culture medium for CSS constructs. (I) depicts total cell-assodated protein expression determined with the HiBit luminescence assay fbr TRAMP constructs, and (J) depicts total exported protein detected in the culture medium fbr TRAMP constructs. Numbers depicted at x-axis Indicate RNA construct number.

[0258] FIG. 18 depicts ELISA endpoint reciprocal titers for day 35 serum samples of mice Immunized twice with lug of RH5 encoding constructs. Negative control samples are from mice immunized with a construct encoding CSP. Numbers depicted at x-axis indicate RNA construct number.

[0259] FIG. 19, parts (A) through (D), Includes schematics of exemplary polypeptides encoded by polyribonucleotides provided herein. All amino add (aa) references included refer to the P. falciparum GW? sequence set out in SEQ ID NO: 23. (A) indudes a schematic of an exemplary polypeptide, RNA Construct 77, encoded by a polyribonucleotide described herein. RNA Construct 77 comprises an HSV glycoprotein D (gD) secretory signal (e.g., SEQ ID NO: 42) and a GARP-A region (aa 410-673) (SEQ ID NO: 312). (B) indudes a schematic of an exemplary polypeptide, RNA Construct 78, encoded by a polyribonudeotlde described herein. RNA Construct 78 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), and a GARP-A region (aa 410-673) (SEQ ID NO: 312) comprising a N504Q mutation (SEQ ID NO: 313). (C) indudes a schematic of an exemplary polypeptide, RNA Construct 82, encoded by a polyribonucleotide described herein. RNA Construct 82 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a GARP-A region (aa 410-673) (SEQ ID NO: 312) comprising a N504Q mutation (SEQ ID NO: 312), a glydne-serine linker (e.g., SEQ ID NO: 86), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75). (D) indudes a schematic of an exemplary polypeptide, RNA Construct 84, encoded by a polyribonudeotlde described herein. RNA Construct 84 comprises an HSV gD secretory signal (e.g., SEQ ID NO: 42), a GARP-A region (aa 52-673) (SEQ ID NO: 342) comprising N183Q, N233Q, N242Q, and N504Q mutations (SEQ IDNO: 309), and a glycine-serine linker (e.g., SEQ ID NO: 86), and a HSV gD transmembrane region (e.g., SEQ ID NO: 75).

[0260] FIG. 20, parts (A) through (C), includes schematics of exemplary polypeptides encoded by polyribonucleotides provided herein. All amino add (aa) references included refer to the P. faldpanim"VMNP (e.g., PTRAMP) sequence set out in SEQ ID NO: 4. (A) includes a schematic of an exemplary polypeptide, RNA Construct 133, encoded by a polyribonudeotide described herein. RNA Construct 133 comprises an HSV glycoprotein D (gD) secretory signal (e.g., SEQ ID NO: 42) and a TRAMP region (aa 42-352). (B) indudes a schematic of an exemplary polypeptide, RNA Construct 134, encoded by a polyribonudeotide described herein. RNA Construct 134 comprises an HSV glycoprotein D (gD) secretory signal (e.g., SEQ ID NO: 42) and a TRAMP region (aa 42-352) comprising N112Q, N129Q, N155Q, N170Q, N195Q, N202Q, N253Q, and N305Q mutations. (C) Includes a schematic of an exemplary polypeptide, RNA Construct 135, encoded by a polyribonudeotide described herein. RNA Construct 135 comprises an HSV glycoprotein D (gD) secretory signal (e.g., SEQ ID NO: 42) and a TRAMP region (aa 42-352) comprising N149Q, N195Q, and N202Q mutations.DEFINITIONS

[0261] Compounds of this disclosure include those described generally above and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry", Sth Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents each of which are hereby incorporated by reference.

[0262] Unless otherwise stated, structures depicted herein are meant to include all stereoisomeric (e.g., enantiomeric or diastereomeric) forms of the structure, as well as all geometric or conformational isomeric forms of the structure. For example, the R and S configurations of each stereocenter are contemplated as part of the disclosure. Therefore, single stereochemical Isomers, as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of provided compounds are within the scope of the disclosure. For example, in some cases, provided compounds show one or more stereoisomers of a compound, and unless otherwise indicated, represents each stereoisomer alone and / or as a mixture. Unless otherwise stated, all tautomeric forms of provided compounds are within the scope of the disclosure.

[0263] Unless otherwise Indicated, structures depicted herein are meant to Include compounds that differ only In the presence of one or more Isotoplcalty enriched atoms. For example, compounds having the present structures including replacement of hydrogen by deuterium or tritium, or replacement of a carbon by 13C- or 14C-enrkhed carbon are within the scope of this disclosure.

[0264] About The term “about", when used herein in reference to a value, refers to a value that Is similar, in context to the referenced value. In general, those skilled in the art, familiar with the context, will appreciate the relevant degree of variance encompassed by “about” in that context For example, In some embodiments, the term “about” may encompass a range of values that within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less of the referred value.

[0265] As used herein, the term "agent,* may refer to a physical entity. In some embodiments, an agent may be characterized by a particular feature and / or effect. For example, as used herein, the term "therapeutic agent' refers to a physical entity has a therapeutic effect and / or elicits a desired biological and / or pharmacological effect In some embodiments, an agent may be a compound, molecule, or entity of any chemical class including, for example, a small molecule, polypeptide, nucleic add, saccharide, lipid, metal, or a combination or complex thereof.

[0266] Amino add: In its broadest sense, as used herein, the term "amino acid” refers to a compound and / or substance that can be, is, or has been incorporated into a polypeptide chain, e.g., through formation of one or more peptide bonds. In some embodiments, an amino acid has the general structure H2N-C(H)(R)-C00H. In some embodiments, an amino add is a naturally-occurring amino acid. In some embodiments, an amino acid is a nonnatural amino acid; in some embodiments, an amino add is a D-amlno add; In some embodiments, an amino acid Is an L-amlno add. "Standard amino acid* refers to any of the twenty standard L-amino acids commonly found in naturally occurring peptides. "Nonstandard amino add* refers to any amino add, other than the standard amino acids, regardless of whether it is prepared synthetical or obtained from a natural source. In some embodiments, an amino acid, including a carboxy- and / or amino-terminal amino add in a polypeptide, can contain a structural modification as compared with the general structure above. For example, in some embodiments, an amino add may be modified by methylation, amidation, acetylation, pegylation, glycosylation, phosphorylation, and / or substitution (e.g., of the amino group, the carboxylic add group, one or more protons, and / or the hydroxyl group) as compared with the general structure. In some embodiments, such modification may, for example, alter the circidating half-life of a polypeptide containing the modified amino acid as compared with one containing an otherwise identical unmodified amino add. In some embodiments, such modification does not significantly alter a relevant activity of a polypeptide containing the modified amino add, as compared with one containing an otherwise Identical unmodified amino add. As will be dear from context, in some embodiments, the term "amino acid' may be used to refer to a free amino add; in some embodiments it may be used to refer to an amino add residue of a polypeptide.

[0267] Antigen.-The term "antigen”, as used herein, refers to an agent that (I) elicits an Immune response; and / or (ii) an agent that binds to a T cell receptor (e.gvwhen presented by an MHC molecule) or to an antibody.

[0268] Anti-malaria immuno response. The term "anti-malaria immune response", as used herein, refers to an Immune response directed to one or more antigens derived from Plasmodium.

[0269] Assodated. Two events or entities are "associated" with one another, as that term is used herein, if the presence, level, degree, type and / or form of one is correlated with that of the other. For example, a particular entity (e.g., polypeptide, genetic signature, metabolite, microbe, etc.) is considered to be assodated with a particular disease, disorder, or condition, if its presence, level and / or form correlates with incidence of, susceptibility to, severity of, stage of, etc. the disease, disorder, or condition (e.g., across a relevant population). In some embodiments, two or more entities are physically "assodated” with one another if they interact, directly or indirectly, so that they are and / or remain in physical proximity with one another. In some embodiments, two or more entities that are physically associated with one another are covalently linked to one another; in some embodiments, two or more entities that are physically associated with one another are not covalently linked to one another but are non- covalently associated, for example by means of hydrogen bonds, van der Waals interaction, hydrophobic interactions, magnetism, and combinations thereof.

[0270] Characteristic portion. As used herein, the term "characteristic portion', In the broadest sense, refers to a portion of a polypeptide or region thereof whose presence (or absence) correlates with presence (orabsence) of a particular feature, attribute, or activity of the polypeptide or region thereof. In some embodiments, a characteristic portion of a polypeptide or region thereof is a portion that is found in the polypeptide or region thereof and in related polypeptide or region thereof that share the particular feature, attribute or activity, but not in those that do not share the particular feature, attribute or activity. In certain embodiments, a characteristic portion shares at least one functional characteristic with the intact polypeptide or region thereof. For example, in some embodiments, a "characteristic portion" of a polypeptide or region thereof is one that contains a continuous stretch of amino acids, or a collection of continuous stretches of amino acids, that together are characteristic of the polypeptide or region thereof. In some embodiments, each such continuous stretch generally contains at least 2, 5, 10, 15, 20, 50, or more amino acids. In general, a characteristic portion of a polypeptide or region thereof is one that, In addtion to the sequence and / or structural Identity specified above, shares at least one functional characteristic with the relevant intact polypeptide or region thereof. In some embodiments, a characteristic portion may be biologically active. In some embodiments, a fragment as described herein can be a portion. Accordingly, in some embodiments, a characteristic fragment can be a "characteristic portion."

[0271] Combination therapy. As used herein, the term "combination therapy" refers to those situations in which a subject is simultaneously exposed to two or more therapeutic regimens (e.g., two or more therapeutic agents (e.g., two or more antibody agents)). In some embodiments, the two or more regimens may be administered simultaneously; in some embodiments, such regimens may be administered sequentially (e.g., all "doses" of a first regimen are administered prior to administration of any doses of a second regimen); In some embodiments, such agents are administered in overlapping dosing regimens. In some embodiments, administration of combination therapy may involve administration of one or more agent(s) or modality(ies) to a subject receiving the other agent(s) or modallty(les) in the combination. For clarity, combination therapy does not require that Individual agents be administered together In a single composition (or even necessarily at the same time), although In some embodiments, two or more agents, or active moieties thereof, may be administered together In a combination composition.

[0272] Comparable; As used herein, the term "comparable" refers to two or more agents, entitles, situations, sets of conditions, etc., that may not be Identical to one another but that are sufficiently slmiar to permit comparison there between so that one skilled In the art will appreciate that conclusions may reasonably be drawn based on differences or similarities observed. In some embodiments, comparable sets of conditions, circumstances, individuals, or populations are characterized by a plurality of substantially identical features and one or a small number of varied features. Those of ordinary skill in the art will understand, in context, what degree of identity is required in any given circumstance for two or more such agents, entities, situations, sets of conditions, etc. to be considered comparable. For example, those of ordinary skill in the art will appreciate that sets of circumstances, individuals, or populations are comparable to one another when characterized by a sufficient number and type of substantially identical features to warrant a reasonable conclusion that differences in results obtained or phenomena observed under or with different sets of circumstances, individuals, or populations are caused by or indicative of the variation in those features that are varied.

[0273] Corresponding toe As used herein, the term "corresponding to" refers to a relationship between two or more entities. For example, the term "corresponding to' may be used to designate the position / identity of a structural element in a compound or composition relative to another compound or composition (e.g., to an appropriate reference compound or composition). For example, in some embodiments, a monomeric residue in apdymer (e.g., an amino add residue in a polypeptide or a nucleic acid residue in a polynucleotide) may be identified as "corresponding to" a residue in an appropriate reference polymer. For example, those of ordinary skill will appreciate that, for purposes of simplicity, residues in a polypeptide are often designated using a canonical numbering system based on a reference related polypeptide, so that an amino add "corresponding to” a residue at position 190, for example, need not actually be the 190thamino add in a particular amino add chain but rather corresponds to the residue found at 190 in the reference polypeptide; those of ordinary skill in the art readily appreciate how to identify "corresponding" amino acids. For example, those skilled in the art wil be aware of various sequence alignment strategies, including software programs such as, for example, BLAST, CS-BLAST, CUSASW++, DIAMOND, FASTA, GGSEARCH / GLSEARCH, Genoogle, HMMER, HHpred / HHsearch, IDF, Infernal, KLAST, USEARCH, parasai, PSI-BLAST, PSI-Search, ScalaBLAST, Sequilab, SAM, SSEARCH, SWAPHI, SWAPHI-LS, SWIMM, or SWIPE that can be utilized, for example, to identify "corresponding" residues In polypeptides and / or nudeic acids in accordance with the present disdosure. Those of skill in the art wil also appreciate that, in some instances, the term "corresponding to” may be used to describe an event or entity that shares a relevant similarity with another event or entity (e.g., an appropriate reference event or entity). To give but one example, a gene or protein in one organism may be described as "corresponding to” a gene or protein from another organism in order to indicate, in some embodiments, that it plays an analogous role or performs an analogous function and / or that it shows a particular degree of sequence Identity or homology, or shares a particular characteristic sequence element

[0274] Dosing regimen-. Those skilled in the art will appredate that the term "dosing regimen” (or "therapeutic regimen”) may be used to refer to a set of unit doses (typically more than one) that are administered Individually to a subject, typically separated by periods of time. In some embodiments, a given therapeutic agent has a recommended dosing regimen, which may involve one or more doses.

[0275] Encodes, ks used herein, the term "encode" or "encoding" refers to sequence information of a first molecule that guides production of a second molecule having a defined sequence of nucleotides (e.g., a polyribonucleotide) or a defined sequence of amino adds. For example, a DMA molecule can encode an RNA molecule (e.g., by a transcription process that Indudes a DNA-dependent RNA polymerase enzyme). An RNA molecule can encode a polypeptide (e.g., by a translation process). Thus, a gene, a cDNA, or an RNA molecule encodes a polypeptide if transcription and translation of RNA corresponding to that gene produces the polypeptide In a cell or other biological system. In some embodiments, a coding region of a polyribonudeotide encoding a target antigen refers to a coding strand, the nudeotide sequence of which is identical to the polyribonucleotide sequence of such a target antigen. In some embodiments, a coding region of a polyribonudeotide encoding a target antigen refers to a non-coding strand of such a target antigen, which may be used as a template for transcription of a gene or cDNA.

[0276] Expression-. As used herein, the term "expression" of a nucleic acid sequence refers to the generation of a gene product from the nudeic add sequence. In some embodiments, a gene product can be a transcript, e.g., a polyribonucleotide as provided herein. In some embodiments, a gene product can be a polypeptide. In some embodiments, expression of a nudeic add sequence involves one or more of the following: (1) production of an RNA template from a DNA sequence (e.g., by transcription); (2) processing of an RNA transcript (e.g., by splidng, editing, etc.); (3) translation of an RNA into a polypeptide or protein; and / or (4) post-translational modification of a polypeptide or protein.

[0277] Heterologous: As used herein, the term "heterologous", with respect to secretory signal or transmembrane region, refers to a secretory signal or transmembrane region from a virus or an organism other than Piasmocfium.

[0278] Homology*. As used herein, the term "homology” or "homolog" refers to the overafl relatedness between polynucleotide molecules (e.g., DNA molecules and / or RNA molecules) and / or between polypeptide molecules. In some embedments, polynucleotide molecules (e.g., DNA molecules and / or RNA mdecides) and / or polypeptide molecules are considered to be "homologous" to one another if their sequences are at least 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical. In some embodiments, polynucleotide molecules (e.g., DNA molecules and / or RNA molecules) and / or polypeptide molecules are considered to be "homologous" to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% similar (e.g., containing residues with related chemical properties at corresponding positions). For example, as is well known by those of ordinary skill in the art, certain amino acids are typically classified as similar to one another as "hydrophobic" or "hydrophilic" amino acids, and / or as having "polar' or "non-polar” side chains. Substitution of one amino add for another of the same type may often be considered a "homologous” substitution.

[0279] Identity. As used herein, the term “identity" refers to the overall relatedness between polynucleotide molecules DNA molecules and / or RNA molecules) and / or between polypeptide molecules. In some embodiments, polynucleotide molecules (eg., DNA molecules and / or RNA molecules) and / or between polypeptide molecules are considered to be "substantially Identical" to one another If their sequences are at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% Identical. Calcination of the percent Identity of two nudeic add or polypeptide sequences, for example, can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second sequence for optimal alignment and non-ldentlcal sequences can be disregarded for comparison purposes). In certain embodiments, the length of a sequence aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or substantially 100% of the length of a reference sequence. The nucleotides at corresponding positions are then compared. When a position In the first sequence is occupied by the same residue (e.g., nudeotide or amino add) as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which needs to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. For example, the percent Identity between two nudeotide sequences can be determined using the algorithm of Meyers and Miller, 1989, which has been incorporated into the ALIGN program (version 2.0). In some exemplary embodiments, nucleic acid sequence comparisons made with the ALIGN program use a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The percent identity between two nudeotide sequences can, alternatively, be determined using the GAP program in the GCG software package using an NWSgapdna.CMP matrix.

[0280] Jhcneaswt Induced, or Reduced.* As used herein, these terms or grammatically comparable comparative terms, indicate values that are relative to a comparable reference measurement. For example, in some embodiments, an assessed value achieved with a provided composition (e.g., a pharmaceutical composition) may be"increased" relative to that obtained with a comparable reference composition. Alternatively or additionally, in some embodiments, an assessed value achieved in a subject may be "increased" relative to that obtained in the same subject under different conditions (e.g., prior to or after an event; or presence or absence of an event such as administration of a composition (e.g., a pharmaceutical composition) as described herein, or in a different, comparable subject (e.g., in a comparable subject that differs from the subject of interest in prior exposure to a condition, e.g., absence of administration of a composition (e.g., a pharmaceutical composition) as described herein.). In some embodiments, comparative terms refer to statistically relevant differences (e.g., that are of a prevalence and / or magnitude sufficient to achieve statistical relevance). Those skilled in the art will be aware, or will readiy be able to determine, in a given context, a degree and / or prevalence of difference that is required or sufficient to achieve such statistical significance. In some embodiments, the term "reduced" or equivalent terms refers to a reduction in the level of an assessed value by at least 5%, at least 10%, at least 20%, at least 50%, at least 75% or higher, as compared to a comparable reference. In some embodiments, the term "reduced” or equivalent terms refers to a complete or essentially complete inhibition, i.e., a reduction to zero or essentially to zero. In some embodiments, the term "increased” or "Induced” refers to an increase In the level of an assessed value by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 80%, at least 100%, at least 200%, at least 500%, or higher, as compared to a comparable reference.

[0281] in order: As used herein with reference to a polynucleotide or polyribonucleotide, "In order" refers to the order of features from 5' to 3' along the polynucleotide or polyribonucleotide. As used herein with reference to a polypeptide, "in order” refers to the order of features moving from the N-termlnal-most of the features to the C- termlnal-most of the features along the polypeptide. "In order” does not mean that no additional features can be present among the listed features. For example, If Features A, B, and C of a polynucleotide are described herein as being "In order, Feature A, Feature B, and Feature C,” this description does not exclude, e.g., Feature D being located between Features A and B.

[0282] Isolated. The term "Isolated'' means altered or removed from the natural state. For example, a nucleic add or a peptide naturally present in a living animal is not "Isolated," but the same nucleic add or peptide partiaHy or completely separated from the coexisting materials of Its natural state is "Isolated." An Isolated nucleic add or protein can exist in substantiaRy purified form, or can exist in a non-native environment such as, for example, a host cell.

[0283] Linker. As used herein, the term "tinker" refers to a portion of a polypeptide that connects different regions, portions, or antigens to one another.

[0284] Lipid*. As used herein, the terms "lipid" and "lipid-lke material" are broadly defined as molecules which comprise one or more hydrophobic moieties or groups and optionally also one or more hydrophilic moleties or groups. Molecules comprising hydrophobic moieties and hydrophilic moieties are also typically denoted as amphiphiles.

[0285] Merozoite stage spedfic Ptasmodium antigen: As used herein, the term "merozoite stage specific Plasmodium antigen" refers to an antigen that is expressed during the merozoite stage of the Plasmodium life cyde. In some embodiments, a merozoite stage spedfic Plasmodium antigen is a Rh5 invasion complex antigen.

[0286] Multimerization region*. As used herein, the term "multimerization region" refers to a region that directs assembly of multimers into a complex, where each multimer comprises a polypeptide associated with the multimerization region.

[0287] RNA lipid nanopartider. As used herein, the term "RNA lipid nanopartfcle* refers to a nanopartide comprising at least one lipid and RNA molecule(s), e.g., one or more polyribonucleotides as provided herein. In some embodiments, an RNA lipid nanopartide comprises at least one cationic amino lipid. In some embodiments, an RNA lipid nanopartide comprises at least one cationic amino lipid, at least one helper lipid, and at least one polymer- conjugated lipid (e.g., PEG-conjugated lipid). In various embodiments, RNA lipid nanoparticles as described herein can have an average size (.e.g., Z-average) of about 100 nm to 1000 nm, or about 200 nm to 900 nm, or about 200 nm to 800 nm, or about 250 nm to about 700 nm. In some embodiments of the present disclosure, RNA lipid nanopartides can have a particle size (e.g., Z-average) of about 30 nm to about 200 nm, or about 30 nm to about 150 nm, about 40 nm to about 150 nm, about 50 nm to about 150 nm, about 60 nm to about 130 nm, about 70 nm to about 110 nm, about 70 nm to about 100 nm, about 80 nm to about 100 nm, about 90 nm to about 100 nm, about 70 to about 90 nm, about 80 nm to about 90 nm, or abort 70 nm to about 80 nm. In some embodiments, an average size of lipid nanoparticles is determined by measuring the average partide diameter. In some embodiments, RNA lipid nanopartides may be prepared by mixing lipids with RNA molecules described herein.

[0288] Neutralization*. As used herein, the term "neutralization" refers to an event in which binding agents such as antibodies bind to a biological active site of a parasite such as a receptor binding protein, thereby inhibiting the parasitic Infedion of cells. In some embodiments, the term "neutralization" refers to an event in which binding agents eliminate or significantly reduce ability of Infecting cells.

[0289] Nucleic add / Polynucleotide.* As used herein, the term "nucleic add" refers to a polymer of at least 10 nucleotides or more. In some embodiments, a nudek add is or comprises DNA. In some embodiments, a nucleic add is or comprises RNA. In some embodiments, a nucleic add Is or comprises peptide nudek add (PNA). In some embodiments, a nudek acid is or comprises a single stranded nudek add. In some embodiments, a nucleic acid is or comprises a double-stranded nucleic add. In some embodiments, a nudek acid comprises both single and doublestranded portions. In some embodiments, a nudek add comprises a backbone that comprises one or more phosphodiester linkages. In some embodiments, a nudek add comprises a backbone that comprises both phosphodiester and non-phosphodlester linkages. For example, in some embodiments, a nudek add may comprise a backbone that comprises one or more phosphorothtoate or S'-N-phosphoramldlte linkages and / or one or more peptide bonds, e.g., as in a "peptide nudek add". In some embedments, a nudek add comprises one or more, or all, natural residues (e.g., adenine, cytosine, deoxyadenosine, deoxycytidine, deoxyguanosine, deoxythymidine, guanine, thymine, uradl). In some embodiments, a nudek add comprises on or more, or all, non-natural residues. In some embodiments, a non-natural residue comprises a nucleoside analog (e.g., 2-aminoadenosine, 2- thiothymidine, inosine, pyrrolo-pyrimidine, 3 -methyl adenosine, 5-methykytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5-bromouridlne, C5-fluorouridfrie, C5-lodouridlne, C5-propynyl-uridlne, C5 - propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8- oxoguanosine, 6-O-methylguanine, 2-thiocytidine, methylated bases, intercalated bases, and combinations thereof). In some embodiments, a non-natural residue comprises one or more modified sugars (e.g., 2'-fluororibose, ribose, 2'-deoxyribose, arabinose, and hexose) as compared to those in natural residues. In some embodiments, a nudek add has a nucleotide sequence that encodes a functional gene product such as an RNA or polypeptide. In some embodiments, a nudek acid has a nucleotide sequence that comprises one or more introns. In some embodiments, a nucleic add may be prepared by isolation from a natural source, enzymatic synthesis (e.g., by polymerization based on a complementary template, e.g., in vivo or in vitro), reproduction in a recombinant cell or system, or chemkalsynthesis. In some embodiments, a nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10,000, 10,500, 11,000, 11,500, 12,000, 12,500, 13,000, 13,500, 14,000, 14,500, 15,000, 15,500, 16,000, 16,500, 17,000, 17,500, 18,000, 18,500, 19,000, 19,500, or 20,000 or more residues or nucleotides long.

[0290] Pharmaceutically effective amount The term "pharmaceutically effective amount" or“therapeutically effective amount" refers to the amount which achieves a desired reaction or a desired effect alone or together with further doses. In the case of the treatment of a particular disease (e.g., malaria), a desired reaction In some embodiments relates to Inhibition of the course of the disease (e.g., malaria). In some embodiments, such inhibition may comprise slowing down the progress of a disease (e.g., malaria) and / or interrupting or reversing the progress of the disease (e.g., malaria). In some embodiments, a desired reaction in a treatment of a disease (e.g., malaria) may be or comprise delay or prevention of the onset of a disease (e.g., malaria) or a condition (e.g., a malaria associated condition). An effective amount of a composition (e.g., a pharmaceutical composition) described herein will depend, for example, on disease (e.g., medaria) or a condition (e.g., a malaria associated condition) to be treated, the severity of such a disease (e.g., malaria) or a condition (e.g., a malaria associated condition), Individual parameters of the patient, Including, e.g., age, physiological condition, size and weight, the duration of treatment, the type of an accompanying therapy (if present), the specific route of administration and similar factors.Accordingly, doses of a composition (e.g., a pharmaceutical composition) described herein may depend on various of such parameters. In the case that a reaction In a patient is Insufficient with an initial dose, higher doses (or effectively higher doses achieved by a different, more localized route of administration) may be used.

[0291] Polypeptide.- As used herein, the term “polypeptide' refers to a polymeric chain of amino adds. In some embodiments, a polypeptide has an amino acid sequence that occurs In nature. In some embodiments, a polypeptide has an amino add sequence that does not occur In nature. In some embodiments, a polypeptide has an amino acid sequence that is engineered In that It is designed and / or produced through action of the hand of man. In some embodiments, a polypeptide may comprise or consist of natural amino adds, non-natural amino acids, or both. In some embodiments, a polypeptide may comprise or consist of only natural amino adds or only non-natural amino adds. In some embodiments, a polypeptide may comprise D-amino adds, L-amino acids, or both. In some embodiments, a polypeptide may comprise only D-amino adds. In some embodiments, a polypeptide may comprise only L-amino acids. In some embodiments, a polypeptide may indude one or more pendant groups or other modifications, e.g., modifying or attached to one or more amino add side chains, at the polypeptide's N-terminus, at the polypeptide's C-termlnus, or any combination thereof. In some embodiments, such pendant groups or modifications comprise acetylation, amidation, lipidation, methylation, pegylation, etc., including combinations thereof. In some embodiments, a polypeptide may be cydic, and / or may comprise a cydic portion. In some embodiments, a polypeptide is not cyclic and / or does not comprise any cydic portion. In some embodiments, a polypeptide is linear. In some embodiments, a polypeptide may be or comprise a stapled polypeptide. In some embodiments, the term "polypeptide" may be appended to a name of a reference polypeptide, activity, or structure; in such instances it is used herein to refer to polypeptides that share the relevant activity or structure and thus can be considered to be members of the same class or family of polypeptides. For each such class, the present specification provides and / or those skilled in the art will be aware of exemplary polypeptides within the dass whoseamino acid sequences and / or functions are known; in some embodiments, such exemplary polypeptides are reference polypeptides for the polypeptide class or family, in some embodiments, a member of a polypeptide class or family shows significant sequence homology or identity with, shares a common sequence motif (e.g., a characteristic sequence element) with, and / or shares a common activity (in some embodiments at a comparable level or within a designated range) with a reference polypeptide of the dass; in some embodiments with all polypeptides within the class). For example, in some embodiments, a member polypeptide shows an overall degree of sequence homology or identity with a reference polypeptide that is at least about 30-40%, and is often greater than about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more and / or includes at least one region (e.g., a conserved region that may in some embodiments be or comprise a characteristic sequence element) that shows very high sequence identity, often greater than 90% or even 95%, 96%, 97%, 98%, or 99%. Such a conserved region usually encompasses at least 3-4 and often up to 35 or more amino adds; in some embodiments, a conserved region encompasses at least one stretch of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or more contiguous amino adds. In some embodiments, a relevant polypeptide may comprise or consist of a fragment of a parent polypeptide. In some embodiments, a polypeptide is a Plasmodium polypeptide construct described herein. A Plasmodium polypeptide construct is a polypeptide that indudes one or more malarial proteins, or one or more portions thereof. In some embodiments, a Plasmodium polypeptide construct described herein Indudes at least one region of Plasmodium Rh5 Invasion complex polypeptide or an antigenic a portion thereof. In some embodiments, a Plasmodium polypeptide construct additionally includes one or more additional amino add sequences, such as a secretory signal (e.g., a heterologous secretory signal), a transmembrane region (e.g., a heterologous transmembrane region), a multlmerization region, and / or a linker, as described herein.

[0292] Prevent As used herein, the term "prevent" or "prevention" when used In connection with the occurrence of a disease, disorder, and / or condition, refers to reducing the risk of developing the disease, disorder and / or condition and / or to delaying onset of one or more characteristics or symptoms of the disease, disorder or condition. Prevention may be considered complete when onset of a disease, disorder or condition has been delayed for a predefined period of time. In some embodiments, prevention refers to reducing the risk of developing clinical malaria.

[0293] Referencer. As used herein, the term "reference" describes a standard or control relative to which a comparison is performed. For example, in some embodiments, an agent, animal, individual, population, sample, sequence or value of interest is compared with a reference or control agent, animal, individual, population, sample, sequence or value. In some embodiments, a reference or control is tested and / or determined substantially simultaneously with the testing or determination of Interest In some embodiments, a reference or control Is a historical reference or control, optionally embodied in a tangible metfium. Typically, as would be understood by those skilled in the art, a reference or control is determined or characterized under comparable conditions or circumstances to those under assessment Those skilled in the art will appreciate when sufficient similarities are present to justify reliance on and / or comparison to a particular possible reference or control.

[0294] Rh5 invasion complex-. As used herein refers to a complex that is present in Plasmodium merozoites that includes Rh5. In some embodiments, a Rh5 invasion complex facilitates merozoite binding to and / or invasion of an erythrocyte. Without limitation, polypeptides in an Rh5 invasion complex may include one or more of Plasmodium reticulocyte -binding protein homolog 5 (Rh5), Plasmodium Cysteine-Rich Protective Antigen (CyRPA), PlasmodiumRh5-interacting Protein (Ripr), Plasmodium Pl 13, Absmod't / m thrombospondin-related apical merozoite protein (TRAMP), and Plasmodium cysteine-rich small secreted protein (CSS). Exemplary Rh5 invasion complexes include the RCR complex and the PCRCR complex. An RCR complex is a trimeric complex comprising Rh5, cysteine-rich protective antigen (CyRPA), and Rh5-interacting protein (Ripr). A PCRCR complex is a pentameric complex comprising Rh5, cysteine-rich small secreted (CSS), Ripr, CyRPA, and Piasmodum thrombospondin-related apical merozoite protein (PTRAMP).

[0295] RibonucMc add (RNA) or Polyribonucleotide: As used herein, the term "ribonucleic add," "RNA,” or "polyribonudeotide" refers to a polymer of ribonucleotides. In some embodiments, an RNA is single stranded. In some embodiments, an RNA Is double stranded. In some embodiments, an RNA comprises both single and double stranded portions. In some embodiments, an RNA can comprise a backbone structure as described In the definition of "Nudeic add / Polynudeotide” above. An RNA can be a regulatory RNA (e.g., siRNA, microRNA, etc), or a messenger RNA (mRNA). In some embodiments, an RNA is a mRNA. In some embodiments, where an RNA is a mRNA, a RNA typically comprises at its 3' end a poly(A) region. In some embodiments, where an RNA is a mRNA, an RNA typically comprises at its 5* end an art-recognized cap structure, e.g., for recognizing and attachment of a mRNA to a ribosome to initiate translation. In some embodiments, a RNA is a synthetic RNA. Synthetic RNAs indude RNAs that are synthesized rh vitro (e.g., by enzymatic synthesis methods and / or by chemical synthesis methods). In some embodiments, a polyribonucleotide encodes a polypeptide, which Is preferably Is a Plasmodium polypeptide construct

[0296] Ribonudeotide: As used herein, the term ’ribonucleotide" encompasses unmodified ribonudeotldes and modified ribonudeotldes. For example, unmodified ribonudeotldes Indude the purine bases adenine (A) and guanine (G), and the pyrimidine bases cytosine (C) and uracil (U). Modified ribonucleotides may include one or more modifications Including, but not limited to, for example, (a) end modifications, e.g., 5' end modifications (e.g., phosphorylation, dephosphorylation, conjugation, Inverted linkages, etc.), 3' end modifications (e.g., conjugation, inverted linkages, etc.), (b) base modifications, e.g. , replacement with modified bases, stabilizing bases, destabilizing bases, or bases that base pair with an expanded repertoire of partners, or conjugated bases, (c) sugar modifications (e.g., at the 2' position or 4' position) or replacement of the sugar, and (d) intemudeoside linkage modifications, Including modification or replacement of the phosphodiester linkages. The term "ribonucleotide" also encompasses ribonucleotide triphosphates including modified and non-modified ribonucleotide triphosphates.

[0297] Secretory signal: &s used herein, the term "secretory signal" refers to an amino add sequence motif that targets associated polypeptides for translocation to a secretory pathway.

[0298] Subject As used herein, the term "subject" refers to an organism to be administered with a composition described herein, e.g., for experimental, diagnostic, prophylactic, and / or therapeutic purposes. Typical subjects indude animals (e.g., mammals such as mice, rats, rabbits, non-human primates, domestic pets, etc.) and humans. In preferred embodiments, a subject is a human subject. In some embodiments, a subject is suffering from a disease, disorder, or condition (e.g., malaria and / or a malaria-associated condition). In some embodiments, a subject is susceptible to a disease, disorder, or condition (e.g., malaria and / or a malaria-assodated condition). In some embodiments, a subject displays one or more symptoms or characteristics of a disease, disorder, or condition (e.g., malaria and / or a malaria-associated condition). In some embodiments, a subject displays one or more nonspecific symptoms of a disease, disorder, or condition (e.g., malaria and / or a malaria-assodated condition). In some embodiments, a subject does not display any symptom or characteristic of a disease, disorder, or condition (e.g.,malaria and / or a malaria-assodated condition). In some embodiments, a subject is someone with one or more features characteristic of susceptibility to or risk of a disease, disorder, or condition (e.g., malaria and / or a malaria- assodated condition). In some embodiments, a subject is a patient. In some embodiments, a subject is an individual to whom diagnosis and / or therapy is and / or has been administered.

[0299] Suffering from*. An indvidual who is "suffering from” a disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition) has been diagnosed with and / or displays one or more symptoms of a disease, disorder, and / or condition.

[0300] Susceptible te An individual who is "susceptible to" a disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition) is one who has a higher risk of developing the disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition ) than does a member of the general public. In some embodiments, an individual who is susceptible to a disease, disorder and / or condition (e.g., malaria and / or a malaria-associated condition) may not have been diagnosed with the disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition). In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition) may exhibit symptoms of the disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition). In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition) may not exhibit symptoms of the disease, disorder, and / or condition (e.g., malaria and / or a malaria-assodated condition). In some embodiments, an Individual who is susceptible to a disease, disorder, and / or condttion (e.g., malaria and / or a malaria-assodated condition) will develop the disease, disorder, and / or condition (e.g., malaria and / or a malaria- assodated condition). In some embodiments, an Individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or a malaria-assodated condition) will not develop the disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition).

[0301] Therapy. The term "therapy" refers to an administration or delivery of an agent or intervention that has a therapeutic effect and / or elicits a desired biological and / or pharmacological effect (e.g., has been demonstrated to be statistically likely to have such effect when administered to a relevant population). In some embodiments, a therapeutic agent or therapy is any substance that can be used to alleviate, ameliorate, relieve, inhibit, prevent, delay onset of, reduce severity of, and / or reduce incidence of one or more symptoms or features of a disease, disorder, and / or condition (e.g., malaria and / or a malaria-assodated condition). In some embodiments, a therapeutic agent or therapy is a medical intervention that can be performed to alleviate, relieve, inhibit, present, delay onset of, reduce severity of, and / or reduce incidence of one or more symptoms or features of a disease, disorder, and / or condition.

[0302] Transmembrane region; As used herein, the term "transmembrane region" refers to a region of a polypeptide that spans a biological membrane, such as the plasma membrane of a cell.

[0303] Theati As used herein, the term "treat,” "treatment," or "treating" refers to any method used to partially or completely alleviate, ameliorate, relieve, inhibit, prevent, delay onset of, reduce severity of, and / or reduce inddence of one or more symptoms or features of a disease, disorder, and / or condition (e.g., malaria and / or a malaria-associated condition). Treatment may be administered to a subject who does not exhibit signs of a disease, disorder, and / or condition (e.g., malaria and / or a malaria-assodated condition). In some embodiments, treatment may be administered to a subject who exhibits only early signs of the disease, disorder, and / or condition (e.g., malaria and / or a malaria-assodated condition), for example for the purpose of decreasing the risk of developingpathology associated with the disease, disorder, and / or condition. In some embodiments, treatment may be administered to a subject at a later-stage of disease, disorder, and / or condition (e.g., malaria and / or a malaria- assodated condition).

[0304] Variant: As used herein, the term "variant" refers to a molecule that shows significant structural (e.g., primary or secondary) identity with a reference molecule but differs structurally from the reference molecule. For example, a variant polypeptide or nucleic add may differ from a reference polypeptide or nudeic add as a result of one or more differences in amino acid or nucleotide sequence and / or one or more differences in chemical moieties (e.g., carbohydrates, lipids, phosphate groups) that are covalently components of the polypeptide or nudeic add (e.gvthat are attached to the polypeptide or nudeic acid backbone).DETAILED DESCRIPTION OF CERTAIN EMBODIMENTSMalaria

[0305] Malaria is a mosquito-borne infectious cfisease caused by single-celled eukaryotic Plasmodium parasites that are transmitted by the bite of Anopheles app. mosquitoes (Phillips, M., etai. Malaria. Nat Rev Dis Primers3, 17050, 2017, which is incorporated herein by reference in its entirety). Mosquitoes that transmit malaria must have been infected through a previous blood meal taken from an infected subject (e.g., a human). When a mosquito bites an infected subject a small amount of blood is taken in containing Malaria parasites. The infected mosquito can then subsequently bite a non-infected subject, infecting the subject

[0306] Malaria remains one of the most serious infectious diseases, causing approximately 200 million dinical cases and 500,000-600,000 deaths annuaHy. Although significant effort has been invested in developing therapeutic treatments for malaria, many malaria parasites have developed resistance to available therapeutics. According to Malaria Eradication Research Agenda Initiative, malaria eradication will only be achievable through effective vaccination.

[0307] In 2015, the European Medicines Agency gave a positive review to a malaria vaccine candidate known as *RTS,S", a milestone in malaria vaccine development. In 2019, the World Health Organization launched pilot programs that provide RTS,S to children at least 5 months of age in parts of three sub-Saharan African countries. RT5,S / AS01 Is an adjuvanted protein subunit vaccine that consists of a portion of the major repeat region and the C- terminus of CSP from Plasmodium falciparum fused to the Hepatitis B surface antigen (HBsAg). The vaccine is a mix of this ACSP-HBsAg compound with HBsAg that forms virus-like particles (RTS,S / AS01; Mosquirix™). RTS,S is administered according to a regimen that requires four doses: an initial 3-dose schediie given at least 1 month apart, and a 4th dose 15-18 months after dose 3 (see, for example, Vandoolaeghe & Schuerman Expert Rev Vaccines. 15:1481, 2016; PATH_MVI_RTSS_Fact Sheet_042019, each of which Is incorporated herein by reference In its entirety). Reports indicate that RTS,S protects approximately 30% to 50% of children from clinical disease over 18 months. RTS,S has been reported to induce protective antibody and CD4+ T-cell responses, but only negligible CD8+ T cell responses (see, for example, Moris et al. Hum Vaccki Immunother 14:17, 2018, which is incorporated herein by reference in Its entirety). Phase III studies of RTS,S delivered as a three-dose series with a booster after 1 yr (year) showed moderate vaccine efficacy in children aged 5 to 17 months preventing 36% of clinical malaria cases over the ful study period with a median follow-up of 4 yrs, with a range of 20% in high to 66% In low transmission settings. Furthermore, published literature suggests that protection wanes over time InducHng reports of potential negative efficacy after 5 yrs In children with high malaria exposure (Olotu et al. 2016, N. Engl. J. Med. 374:2519-29)which is incorporated herein by reference in its entirety).Thus, an effective malaria vaccine remains an unmet medical need of critical importance for global health.Lifecycle

[0308] During a blood meal, infected mosquitos inject, along with their anticoagulating saliva, sporozoites known as the liver stage of Plasmodium spp. Sporozoites journey through the skin, and if successful, into hepatocytes of the liver. This journey happens very quickly; it can be completed within only a few minutes (Sinnis et al., Parasite! Int. 2007 Sep;56(3): 171-8, which is incorporated herein by reference in its entirety). This is a time known to be a stage during which it is challenging for the host immune system to mount an effective response against the parasite, as only a small number (thought to be a few hundred at maximum) of sporozoites are injected by the mosquito, with a small fraction of those parasites establishing Infection In the liver (Flores-Garda et al., mBio. 2018 Nov 20;9(6):e02194-18, which is incorporated herein by reference in its entirety).

[0309] When moving from an inoculation site in the skin to the liver, sporozoites traverse host ceHs (Mota et al., Science 2001 Jan 5;291(5501): 141-4). Sporozoites traverse different types of host cells at the dermis, including fibroblasts and phagocytes (Amino et al.. Cell Host Microbe. 2008 Feb 14;3(2):88-96, which is incorporated herein by reference in its entirety), and the liver sinusoidal barrier, containing liver endothelial cells and Kupffer cells (Frevert et al., PLoS Biol 3(6): el92. 2005, which is incorporated herein by reference In its entirety) and sinusoidal endothelial cells (Tavares et al., J Exp Med 2013 May 6;210(5):905-15, which is Incorporated herein by reference In Its entirety), in order to gain access to hepatocytes. Sporozoites preferentially traverse cells with low-sulfated heparin sulfate proteoglycans (HSPGs) but preferentially Invade cells with high-sulfated HSPGs (Coppi et al., Cell Host & Microbe 2, 316-327, November 2007, which Is Incorporated herein by reference In Its entirety).

[0310] Cell traversal was first observed as non-phagocytic entry of P. Aergite / sporozoltes Into macrophages followed by "escape" from these cels (Vanderberg et al., J. Euk. Microbiol. 37:528-536, 1990, which is Incorporated herein by reference In Its entirety). The biochemical, biophysical, and stepwise processes of traversal are still being explored. However, It has been suggested by electron microscopy that host cell rupture occurs upon entry and exit from the host cell (Mota et al., 2001; Tavares et al., 2013, each of which is incorporated herein by reference in its entirety). It has also been shown that P. yoetiispotozoktes can enter hepatocytes via a transient vacuole and that host membrane rupture occurs upon cell exit rather than cell entry (Risco-Castillo et al., Cell Host Microbe 2015 Nov ll;18(5):593-603, which is incorporated herein by reference in its entirety).

[0311] Sporozoites also traverse hepatocytes before establishing a productive hepatocyte infection (Mota et al., 2001, which is incorporated herein by reference in its entirety). Several possibilities emerged as to why this occurs. The first hypothesis suggested that migration through hepatocytes primes parasites for invasion by activating apical exocytosis (Mota et al., Nat Med 2002 Nov;8(ll): 1318-22, which is incorporated herein by reference in Its entirety). The second theory suggested that traversal releases hepatocyte growth factor (HGF), making neighboring hepatocytes more susceptible to infection (Carrolo et al., Nat Med . 2003 Nov;9(ll):1363-9, which is incorporated herein by reference in its entirety). Lastly, other studies suggest that it takes some time for sporozoites to switch off the machinery for traversal and activate invasion machinery (Amino et al., 2008, Coppi et al., 2007, each of which is incorporated herein by reference in its entirety), and that traversal primarily functions to penetrate cell banners and avoid phagocytosis en route to the liver (Amino et al., 2008, Coppi et al., 2007, Tavares et al., 2013, each of which is incorporated herein by reference in its entirety).

[0312] Although it has been shown that sporozoites traverse human cells (Behet et al., Malar J 2014 Apr 5;13: 136; Cha et al., J Exp Med 2015 Aug 24;212(9):139M03; Dumoulin et al., PLoS One 2015 Jun 12;10(6):e0129623; van Schaijk et al., PLoS ONE, 3 (10). e3549 2008, each of which is incorporated herein by reference in its entirety), the molecular basis for the traversal process is largely unstudied. Antibodies against circumsporozoite protein (CSP) impair traversal (Dumoulin et al., 2015, which is incorporated herein by reference in its entirety), but this is likely due to inhibition of motility rather than a direct effect (Cha et al., J Exp Med 2016 Sep 19;213(10):2099-112, which is incorporated herein by reference in its entirety). Furthermore, antibodies induced by CPS-immunication (chloroquine prophylaxis with sporozoites) may target CSP and interfere with cell traversal (Behet et al., 2014, which is Incorporated herein by reference in its entirety). Recently it was shown that glyceraldehyde 3- phosphate dehydrogenase (GAPDH) on the parasite surface Interacts with CD68 on Kupffer cells during traversal (Cha et al., 2015, Cha et al., 2016, each of which is incorporated herein by reference in its entirety).

[0313] In rodent malaria parasites such as P. berghei, two sporozoite miaroneme proteins have been identified that appear to be essential for cel traversal (sporozoite microneme protein essential for cell traversal [SPECT1; Ishino et al., PLoS Biol., 2 (2004), pp. 77-84, which is incorporated herein by reference in its entirety] and SPECT2 [Ishino et al., Cell. Microbiol., 7 (2005), pp. 199-208, which is incorporated herein by reference in its entirety], also called perforin-like protein 1 [PLP1] [Kaiser et al., Mol. Blochem. Parasitol., 133 (2004), pp. 15-26, which is Incorporated herein by reference In Its entirety]. Even though genetic disruption of SPECT1 or SPECT2 rendered sporozoites unable to traverse murine cells, they still invaded hepatocytes in vitro (Ishino et al., 2004, Ishino et al., 2005, each of which Is Incorporated herein by reference in its entirety). When Injected Into rodents, sporozoites lacking SPECT1 or SPECT2 were Impaired for liver infection, but a small number of sporozoites could stIH establish liver infection that resulted in subsequent patency. However, depletion of Kupffer cells aflowed mutants to establish liver infection at levels comparable with wild-type parasites (Ishino et al., 2004, Ishino et al., 2005, each of which Is incorporated herein by reference In its entirety). This data suggests that traversal by rodent-infecting sporozoites Is Important for navigating through the sinusoidal layer, but not for hepatocyte invasion, malarial exoerythrocytic forms development, or growth within erythrocytes (Ishino et al., 2004, Ishino et al., 2005, each of which is Incorporated herein by reference In its entirety).

[0314] The ortholog of SPECT2 in P. yoeSi, PLP1, has been shown to play a role in cell traversal. Although this protein is not required for hepatocyte entry, it plays a role in egress from transient vacuoles during traversal (Risco- Castillo et al., 2015, each of which is incorporated herein by reference in its entirety). Thus, sporozoites that infect rodents can traverse host cells by generating a vacuole at the entry step and use a perforin-like protein (e.g., SPECT2 / PLP1) to escape from this compartment and / or a host cell, during cell exit.

[0315] Once sporozoites have Invaded liver cells, they dfferentiate into merozoites, a replicative form of the parasite. Within a few days, a single sporozoite can lead to 5,000-10,000 merozoites. Merozoites bud from the host hepatocyte in structures called merosomes, which contain up to a thousand merozoites and are hidden from host immune responses due to their host membrane composition. These merosomes ultimately release merozoites that mix freely with the host cytoplasm and appear in the blood stream, where they invade red blood cells and begin the blood stage of infection, characterized by fast asexual replication and clinical presentation. Within a small number of days, hundreds of thousands of parasites can be present in the blood.

[0316] Plasmodium spp. parasites gain entry into red blood cells through specific ligand-receptor interactions mediated by proteins on the surface of the parasite that interact with receptors on the host erythrocyte (mature redblood cell) or reticulocyte (immature red blood cell), whereas P. / atoparumcan invade and replicate in erythrocytes and reticulocytes, P. wVaxand other species predominantly invade reticulocytes, which are less abundant than erythrocytes. Most of the erythrocyte-binding proteins or reticulocyte-binding proteins that have been associated with invasion are redundant or are expressed as a family of variant forms; however, for P. falciparum, two essential red blood cell receptors (basigin and complement decay-accelerating factor (also known as CD55)) have been identified.

[0317] P. mar and P. ovale can also enter a dormant state in the liver, the hypnozoite.

[0318] The invasion of a red blood cell by the merozoite involves interactions of multiple parasite derived proteins (e.g., ligands) with red blood cell (RBC) proteins (e.g., receptors) (Weiss et al., Pios Path., 2015 Feb 27; 10.1371, which is Incorporated herein by reference in its entirety). The invasion process begins by the merozoite first attaching to the RBC. Merozoite-RBC Interaction Is further strengthened through merozoite surface protein- 1 (MSP1) and unknown RBC proteins, causing some deformation of the RBC surface. After the deformation, interaction of merozoite EBA and Rh protein families (excluding Rh5) with host receptors like CR1 lead to actin-dependent deformation of the RBC membrane and reorientation of the merozoites apical end onto the RBC surface (Geoghehan et al., Nat Commui., 2021 June 15;10.1038 which is incorporated herein by reference in its entirety). This deformation event increases the surface area of interaction between merozoite and RBC membranes, an interaction which can be stabilized by an Rh5 invasion complex comprising Plasmodium thrombospondin-related apical merozoite protein (PTRAMP), cystelne-rlch small secreted (CSS), cysteine-rich protective antigen (CyRPA), Rh5-interactlng protein (Rlpr) and Rh5. This Rh5 invasion complex including the five proteins is referred to as the PCRCR complex.

[0319] The creation of the PCRCR complex begins in the endoplasmic reticulum, where Its constituents cystelne-rlch small secreted (CSS) protein and Plasmodium thrombospondin-related apical merozoite protein (PTRAMP) Interact to form a heterodimer referred to as PTRAMP-CSS. PTRAMP-CSS Is trafficked to a secretory organelle called the microneme, where CSS interacts with Rh5-interactlng protein (Rlpr) and cystelne-rlch protective antigen (CyRPA) to form a tetrameric complex called PCRC. At some point after deformation occurs, the merozoite Initiates a polarized secretion process that allows the mlcronemal PCRC complex opportunity to Interact with rhoptry protein Rh5, forming the pentameric complex PCRCR. The PCRCR complex, through Rh5, can then bind a host cell receptor, called basigin, broadly across the merozoite-RBC Interphase. PCRCR binding to basigin creates a stable and Irreversible platform between the apical end of the merozoite and the deformed RBC surface, allowing Rh5 and Rlpr to embed into the RBC membrane (Scally et al., Nat Microb., 2022 May 4, which is incorporated herein by reference in its entirety). Once the merozoite-RBC interaction is secured, an open connection between the merozoite's apical tip and the RBC surface is formed which acts as a conduit for Ca2* to flow into the RBC, and for merozoite derived invasion proteins, such as AMA1 and RON2, to help establish the moving junction (Srinivasan et al., Proc Natl Acad Sd., 2011 Jul 25;13275-80, which is Incorporated herein by reference in its entirety). It Is through this moving junction that the parasite, utilizing its actin-myosin dependent gliding motility, propels itself inside the RBC and establishes a parasitopherous vacuole within which the parasite grows and replicates.

[0320] It has been shown that Rh5 binds basigin with higher affinity when complexed with CyRPA and Ripr to form the RCR complex, and has the highest affinity for basigin when part of the PCRCR complex (Wong et al., Nature., 2019 and Scally et al., Nat Microb., 2022 May 4, each of which are incorporated herein by reference in its entirety).

[0321] Merozoites that egress from red blood cells can invade other red blood cells to continue to the asexual blood stage of the parasite lifecycle. A small percentage of schizonts are already committed to a different fate andmerozoites from these schizonts, following invasion of a new red blood cell, will differentiate into the sexual forms on the parasite's life cycle; either male or female, gametocytes. Gametocytes are taken up by the mosquito vector during blood feeding. In the gut of the mosquito, male gametocytes undergo 3 rapid rounds of mitosis to form 8 flagellate microgametes. Female gametocytes mature into macrogametes, egressing from their red blood cell. Male microgametes are motile forms with flagellae and seek the female macrogamete. The male and female gametocytes fuse, forming a diploid zygote, which matures and differentiates into an ookinete; this motile form secretes chitinases and other lytic proteins such as CelTOS in order to disrupt and traverse through the peritrophic matrix and traverse the midgut epithelium to reach the basal lamina where it further differentiates and matures as an oocyst Oocysts mature over approximately 10 days (depending on the temperature), replicating to form sporozoites that egress the mature oocyst Into the hemocoel of the mosquito. Thousands of sporozoites form in a single oocyst and become randomly distributed throughout the hemocoel. It is thought that sporozoites are passively circulated through the mosquito haemolymph until they encounter the salivary glands, where they actively invade the glands. Following invasion of the salivary gland, sporozoites are re-programmed via an unknown mechanism to prepare for Iver Invasion. Evidence of this reprogramming has been demonstrated by the inability of midgut sporozoites (directly from oocysts) to invade hepatocytes, and also by the fact that sporozoites which have successfully invaded a salivary gland are unable to re-invade another salivary gland if presented one. Salivary gland sporozoites alter mosquito behavior and salivary gland function, as less saliva is produced resulting In an Increase In mosquito probing behavior, increasing the chances of transmission to a human host via a mosquito bite and continuing the human host's phase of this parasite's life cyde.

[0322] P. vivax anti P. ovale can also enter a dormant state in the liver, the hypnozoite.

[0323] One particular challenge associated with mounting an immune response capable of clearing sporozoites before a liver infection has been established Is that the most abundant and Immunogenic protein on the sporozoite surface, the circumsporozoite protein (CSP), is only exposed to the immune system in small quantities and for a short duration of time due to the variably low inoculum from the mosquito and the kinetics of hepatocyte infection after inoculation. Furthermore, after liver infection is established, the parasite differentiates into a stage during which it no longer expresses CSP and hstead has a different mosaic of surface antigens, making the parasite Invisible to, e.g., any memory immune response directed towards the liver stage. The early stages of parasite exposure to the human host create a short window for the innate and memory immune systems to generate a response that is capable of clearing all parasites before infection is established. The clinical significance of immune evasion by sporozoites are high at this point, as all it takes is a single sporozoite to invade a hepatocyte and produce as many as 10,000 blood stage parasites (merozoites) capable of invading, replicating within, and lysing red blood cells (Shears et al., jproteome. 2019 July 23; 3404-3418, which Is Incorporated herein by reference In its entirety). These initial stages of the parasite's life cyde in a human host help to demonstrate the difficulty in targeting liver stage parasites for therapeutic intervention and the low efficacy seen with current vaccines. (Oluta A. et al., N Engl J Med. 2016 June 30;216:374, which is incorporated herein by reference in its entirety). Therefore, targeting the blood stage of Plasmodium spp. infection offers a promising approach for reducing deaths caused by malaria.

[0324] Malaria symptoms typically develop 4-8 days after initial red blood cell invasion. Replication cyde of merozoites within the red blood cells continues for 36-72 hours, until hemolysis, releasing the merozoites for another round of red blood cell infection. Thus, in synchronous infections (infections that originate from a single infectious bite), fever occurs every 36-72 hours, when infected red blood cells lyse and release endotoxins en masse.

[0325] Some drugs that prevent Plasmodium spp. invasion or proliferation in the liver have prophylactic activity, drugs that block the red blood cell stage are required for the treatment of the symptomatic phase of the disease, and compounds that inhibit the formation of gametocytes or their development in the mosquito (including drugs that kill mosquitoes feeding on blood) are transmission-blocking agents (Phillips, et al. Malaria. Nat Rev Dis Primers3, 17050 (2017), which is incorporated herein by reference in its entirety). B. Genome

[0326] Since completion of the first sequence of P. falciparum 3D7 genome in 2002, genomic research on malaria parasites has rapidly advanced. Except for a short diploid phase after fertilization in the mosquito midgut, Plasmodium spp. parasites are haploid throughout their life cycle. The genomes of (Afferent species range from 20 to 35 megabases, contain 14 chromosomes, a circular plastid genome of approximately 35 kilobases, and multiple copies of a 6 kilobase mitochondrial DMA. Comparison of genomes from different species showed that homologous genes are often found in synthetic blocks arranged in different orders among different chromosomes.

[0327] The adenine-thymine (AT) content of Plasmodium spp. can also be very different, e.g., ~80% AT in P. falciparum, P. reichenowi, and P. gaHinaceunr, ~75% AT in rodent malaria parasites; and ~60% AT in P. vivax, P. knowtesi, and P. cynomolgi. AT content is often higher in introns and intergenic noncoding regions than in proteincoding exons, with an average of 80.6% AT for the whole P. fakiparum genome versus 86.5% for noncoding sequences. The high AT content of P. fakiparum reflects large numbers of low-complexity regions, simple sequence repeats, and microsatellites, as well as a highly skewed codon usage bias. Polymorphisms of AT-rich repeats provide abundant markers for linkage mapping of drug resistance genes and for tracing the evolution and structure of parasite populations.

[0328] Malaria parasite genomes carry multigene families that serve important roles in parasite interactions with their hosts, including, for example, antigenic variation, signaling, protein trafficking, and adhesion. Among the gene families, genes encoding P. fakiparum erythrocyte membrane protein 1 (P / EMP1) have been studied most extensively. Each Individual P. falciparum parasite carries a unique set of 50 to 150 copies of the vargene In Its genome, where switches of gene expression can produce antigenic variation. P / EMP1 plays an Important role in the pathogenesis of clinical developments such as in cerebral and placental malaria, in which it mediates the cytoadherence of infected red blood cells (iRBCs; infected erythrocytes) in the deep tissues. Different P / EMP1 molecules bind to various host molecules, including o2 -macroglobulin, CD36, chondroitin sulfate A (CSA), complement Iq, CR1, E-selectins and P-selectins, endothelial protein C receptor (EPCR), heparan sulfate, ICAM1, IgM, IgG, PECAM1, thrombospondin (TSP), and VCAM1. Such binding leads to activation of various host inflammatory responses. Hemoglobinopathies, including the hemoglobin C and hemoglobin S trait conditions, interfere with P / EMP1 display In knob structures of the IRBCs. This poor dsplay of P / EMP1 on the host cell surface offers protection against malaria by reducing the cytoadherence and activation of inflammatory processes that promote the development of severe disease.

[0329] Members of the large Plasmodium Interspersed repeat (pir) multigene family are named differently by parasite species, for example, yir in P. yoelii, bir in P. berghei, vir in P. vivax. Several P. falciparum gene families (stevor, rif, and P / MC-2TM) are classified with pir by their similar gene structures, which characteristically Include a short first exon, a long second exon, and a third exon encoding a transmembrane domain. In a recent study, the pir genes from P. chabaudi^df) were shown to be expressed in different cellular locations, within and on the suface of iRBCs, and in merozoites. Malaria parasites devote large portions of their genomes to gene families that ensureevasion of host immune defenses and protection of molecular processes essential to infection. These famiies emphasize the importance of research on their roles in parasite-host interactions and virulence, despite the difficulties inherent to their investigation.

[0330] An additional, exemplary polymorphic gene family comprises a group of 14 genes encoding proteins with six cysteines (6-Cys). These proteins often localize on the parasite surface interacting with host proteins and are expressed at different parasite developmental stages. 6-Cys proteins also demonstrate diverse functions and have been shown to play roles in, for example, parasite fertilization, mating interactions, evasion of immune responses, and invasion of hepatocytes. The proteins expressed in asexual stages are generally polymorphic and / or under selection, suggesting that they could be targets of the host immune response; however, their functions in parasite development remain largely unknown.

[0331] Plasmodium genomes can be highly polymorphic. Early studies demonstrated polymorphisms involving tens to hundreds of kilobases and that the chromosome structure in P. falciparum is largely conserved in central regions but extensively polymorphic is both length and sequence near the telomeres. Much of the subtelomeric variation was explained by recombination within blocks of repetitive sequences and families of genes.

[0332] The frequency of simple sequence repeats (microsatellites) in P. faldparum is estimated to be approximately one polymorphic microsatellite per kb DNA. Without wishing to be bound by any one theory, this high rate may reflect the AT -rich nature of the genome. Mlcrosatellltes seem to be less frequent In other Plasmodium species that have genomes with lower AT contents. In addition to the highly polymorphic and repetitive structure of Plasmodium genomes, there are also large numbers of Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) (Su eta!., Plasmodium tenomks and Genetics: New Insights Into Malaria Pathogenesis, Drug Resistance, Epidemiology, and Evolution. Clin Microbiol Rev. 2019 Jul 31;32(4), which is Incorporated herein by reference In its entirety).C. Plasmodium Proteins1. Rh5 Invasion Complex Polypeptides Rh5

[0333] Rh5 is found In P. faldparum, but not in all other species of Plasmodium that infect humans which contain proteins that perform an analgous function as Rh5. Rh5 orthologues are also found in other species belonging to the Lavarenia subgenus, which includes parasites that infect chimpanzees and gorillas, indicating a unique role in P. falciparum invasion of human erythrocytes. See, e.g., Ragotte, et al. Trends Parasitol. 36(6) 2020, which is incorporated herein by reference in its entirety. Rh5 is expressed during the mature schizont stages and localizes to the Rhoptry, a polarized secretory organelle of P. faldparum. Rh5 is a protein that is secreted during the invasion process and is believed to be essential for the completion of parasite invasion of the erythrocyte. Rh5 functions downstream of intial parasite attachment to the erythrocyte surface and deformation of the erythrocyte membrane. Upon secretion, Rh5 binds to erythrocyte surface protein basigin, creating an attachment and a stable platform for downstream receptor-ligand interactions and associated invasion invents to occur. Bindng of Rh5 to basigin is also required for the induction of a spike in calcium within the erythrocyte, which is blocked when merozoites attempt to invade in the presence of anti-Rh5, anti-Ripr, or anti-baslgin antibodies or soluble basigin (See, e.g., Ragotte (2020), which is incorporated herein by reference in its entirety).

[0334] Rh5 can interact with multiple proteins to form complexes. The affinity of Rh5 for basigin varies based on which complex Rh5 is in. For example, Rh5 can complex with CyRPA and Ripr to form an elongated protein trimer,called RCR, on the merozoite surface that binds to erythrocyte surface protein basigin with higher affinity than Rh5 alone. (See, e.g., Ragotte (2020) and Wong (2019), each of which are incorporated herein by reference in its entirety). Rh5 has its highest affinity to basigin when interacting with PTRAMP, CSS, Ripr, and CyRPA in a pentameric complex known as PCRCR. See, Scally (2022).

[0335] Rh5 is a 63 kDa protein expressed during the mature schizont stage. It is processed and cleaved to a 45 kDa form which is shed by the parasite. The structure of Rh5 reveals a kite-like architecture formed from the coming together of two three-helical bundles. See, e.g., Ragotte (2020), which is incorporated herein by reference in its entirety.

[0336] Rh5 sequences are known (see, e.g., UnIProt accession numbers A0A159SK44, A0A159SK99, A0A159SKS8, A0A159SKW8, A0A159SL23, A0A159SL78, A0A159SL96, A0A159SLM7, A0A159SMC8, A0A159SMR9, A0A161FQT0, A0A1B1UZE2, A0A1B1UZE4, A0A1B1UZE5, A0A346RCI1, A0A346RCJ0, A0A346RCJ2, A0A346RCJ3, A0A346RCJ4, A0A346RCK4, A0A346RCK5, A0A346RCK6, A0A346RCK9, B2L3N7, Q8IFM5, each of which is incorporated herein by reference in its entirety), and exemplary Rh5 amino add sequence is provided in Table 1. Rh5-lnteractino Protein fRiorl

[0337] Rh5-lnteracting Protein (Ripr) is an approximately 120 kDa protein and localized to mkronemes during the schizont stage of the Plasmodium life cycle. The full-length 120 kDa protein is processed into two fragments of similar size, an N-termlnal fragment (Indudlng EGF domains 1 and 2) and a C-termlnal fragment (Indudlng EGF domains 3-10). Ripr colocalizes with Rh5 and CyRPA during parasite invasion at the junction between merozoites and erythrocyte. Parasites with conditional knockouts of fliRipr induce membrane deformation, but cannot complete Invasion (See, e.g., Ragotte (2020) which is incorporated herein by reference in Its entirety).

[0338] Ripr sequences are known (see, e.g., UniProt accession numbers A0A193PDI9, A0A193PDK3, A0A193PDK8, A0A193PDL3, A0A193PDL9, A0A193PDP4, A0A193PDQ8, A0A193PE01, A0A193PE05, A0A193PE07, 097302, A0A193PE17). Exemplary Ripr amino add sequences are provided In Table 1.Cvstelne-Rich Protective Antigen fCvRPAI

[0339] Cysteine-Rich Protective Antigen (CyRPA) is a 43 kDa protein with a predicted N-terminal secretion slgial. CyRPA is a critical mediator of an Invasion multi-protein complex consisting of Rh5 and Ripr, known as RCR, that Improves Rh5 affinity to the erythrocytic basigin receptor. The ability of CyRPA to make limited contact with Ripr and Rh5 is thought to permit the disassociation of Rh5 and Ripr from this complex so they can be inserted into the erythrocyte membrane, helping to further stabilize the contact between parasite and erythrocyte. CyRPA also plays a role in the PCRCR complex which further increase Rh5 affinity to basigin. CyRPA mediated Rh5 binding to basigin is important for stabilizing the parasite-erythrocyte membrane interaction which allows downstream invasion events, like Ca2+increase In the erythrocyte cytosol and establishment of tight / movlng junctions, to occur. CyRPA is highly conserved, with only a single SNP above 5% prevalence in the general population. CyRPA is important for invasion (as conditional knockdown causes the loss of invasion activity), and CyRPA has poor sero-reactivity from natural exposure (See, e.g., Ragotte (2020) and Cowman (2018) each of which is incorporated herein by reference in its entirety).

[0340] CyRPA sequences are known (see, e.g., Uniprot accession number A0A2S1Q7P0, A0A2S1Q7P5, A0A2S1Q7Q4, Q8IFM8, each of which is incorporated herein by reference in its entirety). Exemplary CyRPA amino add sequence is provided in Table 1.Ptesmtxi'u / nThrombowondic- Related Apical Merozoite Protein (PTRAMP)

[0341] Plasmodium thrombospondic-related apical merozoite protein (PTRAMP) is a 352 amino add protein that localizes to developing micronemes and relocates to the merozoite surface upon invasion and is understood to be important for host cell invasion by P. falciparum. Orthologs to the gene encoding PTRAMP is present in all malaria parasite spedes examined, indicating a conserved role in host invasion and making it an opportune target for therapeutic intervention. Important to vaccine approaches, PTRAMP appears to exhibit both linear and conformational epitopes, which would give the immune system the opportunity to utilize both B cell receptors and T cell receptors for recognition and activation when exposed to PTRAMP (Alvaro et al., Malaria Jou., 2010 Oct. 13;10.1186, which is Incorporated herein by reference in its entirety). PTRAMP can interact with cysteine-rich small secreted (CSS) protein to form a heterodimer known as PTRAMP-CSS which in turn can, through CSS, Interact with Ripr and CyRPA to form a tetrameric complex called PCRC, that ultimately Interacts with Rh5 forming a pentameric complex PCRCR which enhances Rh5 binding to host baslgin and Is important for P. falciparum to invade RBCs. Nanobodies against PTRAMP inhibit merozoite significantly reduce merozoite invasion and give evidence to the potential efficacy therapeutically targeting PTRAMP could provide (Scally et al., Nat Microb., 2022 May 4, which Is incorporated herein by reference In Its entirety).

[0342] PTRAMP sequences are known (see, e.g., Uniprot accession number [Q8I5M8]). Exemplary PTRAMP amino acid sequence is provided in Table 1.Cvstelne-Rlch Small Secreted Protein (CSS)

[0343] Cysteine-rich small secreted protein (CSS) Is a 290 amino add cryptic 6-Cys protein comprised of two degenerate 6-Cys domains. Proteins belonging to this family commonly mediate extracellular protein-protein interactions, a role that has been confirmed to occur In P. falciparum. CSS is capable of biding both PTRAMP and Ripr. CSS Interaction with PTRAMP occurs in the endoplasmic reticulum, whereas CSS interaction with Ripr occurs after trafficking to the micronemes. CSS Interaction with PTRAMP and Ripr are involved in Invasion and the formation of the PCRC complex, which is capable of complexing with Rh5 and enhancing Rh5's Interaction with baslgin. Similar to PTRAMP, nanobodies against CSS have been showing to Inhibit Invasion, indicating Its role in the invasion process likely thought its partldpation in the PCRCR complex. Nanobodies which inhibit CSS binding to PTRAMP or Ripr do not inhibit invasion, confirming the interaction of these proteins before exposure to the merozoite surface. The Inhibitory activity of nanobodies against CSS are thought to occur by potentially blocking Ripr and / or Rh5 insertion into the RBC membrane and / or disrupting the conformational changes of the PCRCR complex required for invasion, although the exact mechanism of inhibition is not entirely known. Contrary to this observation and of immunological significance, polydonal antibodies to CSS and PTRAMP do not exhibit any neutralizing activity, indicating the immunodominance of non-neutralizing epitopes of CSS and PTRAMP that bias antibody selection (in a natural setting) away from epitopes with neutralizing capability. This observation provides the molecular rationale for identifying invasion inhibitory epitopes on CSS and PTRAMP which are highly conserved in P. falciparum, for usage in vaccine platforms. See Cowman (2022).

[0344] CSS sequences are known (see, e.g., Uniprot accession number [Q8IM47]). Exemplary CSS amino acid sequence is provided in Table 1.

[0345] In some embodiments, a Plasmodium CSS polypeptide or antigenic portion thereof comprises a serine at position 30, as numbered according to SEQ ID NO: 5. As exemplary CSS amino add sequence comprising a C30S mutation is provided in Table 1.£113

[0346] P113 is a glycosylphosphatidylinositol (GPI)-linked protein that interacts directly with the N terminus of unprocessed Rh5, which has been thought to provide a mechanism by which the Rh5 invasion complex is tethered to the merozoite surface. However, recent findings have shown that P113 may not be essential for P. falciparum growth, as other proteins and complexes exist that can perform the Rh5 membrane tethering function of P113. See, e.g., Ragotte (2020) and Scally (2022). In addition to its canonical role, P113 is present in the paristopherous vacuole (PV) and has been shown to interact with parasite export complexes like PTEX and EPIC, which are important for the transport of parasite effector proteins across the paristopherous vacuole membrane (PVM). P113 has also been shown to play a role in PVM architecture, as the deletion of this gene leads to a disruption In PVM morphology. P113 orthologues are found in all Plasmodium species sequenced thus far, which is suggestive of common and conserved functions (Bullen et al. (2022) Molecular Microbiology 117:1245-1262, which is incorporated herein by reference in its entirety). Despite this fact, in P. berghei, Pl 13 knockout parasites were viable, indicating the protein was not essential for asexual blood stage growth and invasion. The knockout parasites do, however, display defects In natural sporozoite transmission, leading to delayed patency in Infected mice (Offeddu et al. (2014) Mol. Blochem. Parasitology 193: 101-109, which is incorporated herein by reference in its entirety).

[0347] Plasmodium Pl 13 sequences are known (see, e.g., Uniprot accession number Q8ILP3). Exemplary P113 amino acid sequence is provided in Table 1.Table 1: Exemplary Sequences for Rh5 Invasion Complex PolypeptidesSEQ ID Protein Sequence (Amino Add) NO:1 Rh5 (3D7) MIRIKKKLILTIIYIHLFILNRLSFENAIKKTKNQENNLTLLPIKSTEEEKDDIKNGKDIKKEI DNDKENIKTNNAKDHSTYIKSYLNTNVNDGLKYLFIPSHNSFIKKYSVFNQINDGMLLNE KNDVKNNEDYKNVDYKNVNFLQYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYY KHLSYNSIYHKSSTYGKCIAVDAFIKKINETYDKVKSKCNDIKNDLIATIKKLEHPYDINNK NDDSYRYDISEEIDDKSEETDDETEEVEDSIQDTDSNHTPSNKKKNDLMNRTFKKMMDE YNTKKKKLIKCIKNHENDFNKICMDMKNYGTNLFEQLSCYNNNFCNTNGIRYHYDEYIHK ULSVKSKNLNKDLSDMTNILQQSELLLTNLNKKMGSYIYIDTIKFIHKEMKHIFNRIEYHT KIINDKTKIIQDKIKLNIWRTFQKDELLKRILDMSNEYSLF1TSDHLRQMLYNTFYSKEKHL NNIFHHUYVLQMKFNDVPIKMEYFQTYKKNKPLTQ2 Ripr (3D7) MFRIFFTLLIIIUKKTSAIDLIEGIFYEKNEIDKLTFSLDHRVRDNLKTDLILNNNGENDYAY LNKYVYniNRDSTEKIKTFFSHNKDMKSCDYFISKEYNSSDKTNQICYKKTFCGWIPNS EBKTNKITNDKLYCAHFNSTHIIIYYISQPLLLEPHVVYEETFFEKGKNDQINCQGMYISL RSVHVHTHNAILQQETLTfTKNLCDGKNNCKFDFDSIKYENKSLTHYLFFINIQYQCISPL NLQENEMCDVYNDDTHKATCKYGFNKIELLKNVCEENYRCTQDICSVNQFCDGENETCT CKTSLLPSAKNNCEYNDLCTVLNCPENSTCEQIGNGKKAECKCENGKYYHNNKCYTKND LELAIKIEPHKKEKFYKNNLYQGKALKPEYIFMQCENGFSIEVINAYVSCYRVSFNLNKLKY VTESLKKMCDGKTKCAYGNTIDPIDDLNHHNICNNFNTIFKYDYLCVFNNQNITSDKNSH LHSNIPSLYNSSILPDINKSKFHLISRNSRTNQYPHNNISMLEIQNEISSHNSNQFSTDPH TNSNNINNMNIKKVEIFRSRFSSKLQCQGGKINIDKAILKGGEGCNDLLLTNSLKSYCNDL SECDIGUYHFDTYCINDQYLFVSYSCSNLCNKCHNNSTCYGNRFNYDCFCDNPYISKYG NKLCERPNDCESVLCSQNQVCQILPNDKLICQCEEGYKNVKGKCVPDNKCDLSCPSNKV CVIENGKQTCKCSERFVLENGVCICANDYKMEDGINCIAKNKCKRKEYENICTNPNEMCA YNEETDIVKCECKEHYYRSSRGECILNDYCKDINCKENEECSIVNFKPECVCKENLKKNNK GECIYENSCLINEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKCVLEDKCVHNKKCSE NSICVNVMNKEPICVCTYNYYKKDGVCLIQNPCLKDNGGCSRNSECTFKYSKINCTCKEN YKNKDDSCVPNTNEYDESFTFQYNDDASIILGACGMIEFSYIYNQIIWKINNSKESYVFYY DYPTAGNIEVQIKNEIFHTHYLKKKIGNSVIYDDFQVDHQTCIYENVFYYSNQN3 CyRPA (3D7) MIIPFHKKFISFFQIVLWLLLCRSINCDSRHVFIRTELSFIKNNVPCIRDMFFIYKRELYNICLDDLKGEEDETHIYVQKKVKDSWrTLNDLFKETDLTGRPHIFAYVDVEEIIILLCEDEEFSN0. Additional Plasmodium Proteins

[0348] Plasmodium parasites are known to express various proteins at different stages of their lifecycles. Exemplary malarial proteins are described below, and exemplary amino add sequences are provided in Table 2. Circumsporozoite Protein fCSPI

[0348] Circumsporozoite protein (CSP) is a multifunctional protein that is involved in Plasmodium life cycle, as it is required for the formation of sporozoites in the mosquito midgut, the release of sporozoites from the oocyst, invasion of salivary glands, attachment of sporozoites to hepatocytes in the liver, and sporozoite invasion of hepatocytes (see, e.g., Zhao et al. (2016) PLoS ONE 11(8): e0161607, which is incorporated herein by reference in its entirety). CSP is present in all Plasmodium spedes, and although variation exists in the amino add sequence across species, the overall domain structure of a central repeat region and nonrepeat flanking regions is well conserved (see, e.g., Zhao et al. (2016) PLoS ONE 11(8): e0161607; Wahl et al. (2022) J. Exp. Med. 219: e20201313, each of which is incorporated herein by reference in its entirety). CSP sequences are known (see, e.g., UniProt accession numbers A0A2L1CF52, A0A2L,lCF88, C6FGZ3, C6FH2,7 C6FHG7, M1V060, M1V0A3, Ml V0 B0,M1V0C4, M1V0E0, M1V9I4, M1VFN9, M1VKZ2, P02893, Q5EU9, Q5BK2, Q5BK8, Q5EIL3, Q5EIL5, Q5BL8, Q5R2L2, Q7K740, Q8I9G5, Q8I9J3, Q8I9J4). Exemplary CSP amino acid sequences are provided in Table 2. E140

[0350] E140 is found in every Plasmodium species for which a genomic sequence is available, and is well conserved, with amino add identity ranging from 34-92% among spedes. See, e.g., Smith , et al. PLoS one 15.5 (2020): 60232234; http: / / doi: 10.1371 / joumal.pone.023223; and U.S. Patent Publication No. US 2019 / 0117752; each of which are incorporated herein by reference in their entirety. E140 is also highly conserved (95-99%) in P. falciparum sir aixxs isolated from different locations around the world, and exhibits a low mutation frequency. E140 is expressed at different life stages of malaria parasites (spedfically, E140 has been detected in sporozoites, liver, and blood stage parasites).

[0351] Protein structure algorithms predict that the E140 protein has five transmembrane domains, presumable spanring a parasite or host-derived membrane. E140 displays distinct patterns of protein expression In mature sporozoites, late liver, and late schizont stages. It traffics to the anterior and posterior ends of the sporozoite, the parasitophorous vacuole space of the late liver stage and around developing merozoites in the late schizont stage. It is also known to be expressed In mature salivary gland sporozoites as well as oocyst-derived sporozoites and oocysts.

[0352] E140 sequences are known (see, e.g., UnIProt accession numbers A0A650D649, A0A650D653,A0A650D672, A0A650D687, AOA650D690, A0A650D694, A0A650D6A3, A0A650D6B8, A0A650D6L3, A0A650D6L7, Q8I299, each of which Is incorporated herein by reference In its entirety), and an exemplary E140 amino add sequence Is provided In Table 2.CeiTOS

[0353] CeiTOS Is required for sporozoite traversal through Kupffer cells during the liver invasion process.CeiTOS forms a pore from within the cell, allowing for sporozoite egress into the liver. Antibody epitopes have been characterized from Immunized mice and infected human populations (PFand PV). In mouse studies, Immunization with CeiTOS has been shown to provide protection and against challenge. Vaccination with CeiTOS may generate antibodies that can bind the extracellular domain of the pore-forming complex, blocking complete formation of the pore and preventing sporozoite traversal Into the liver. See, e.g., Jimah et al., ELIFEe2016 Dec l;5:e20621. dol: 10.7554 / eUfe.20621, which is incorporated herein by reference in its entirety.

[0354] CeiTOS sequences are known (see, e.g., Uniprot accession number M1ETJ8, Q53UB7, A0A2R4QLA5, A0A2R4QU0, A0A2R4QLI5, A0A2R4QU1, A0A2R4QU4, M1ETJ8, Q53UB8, Q8I5P1, each of which is incorporated herein by reference in its entirety). An exemplary CeiTOS amino add sequence is provided in Table 2.

[0355] SPECT1 and SPECT2 (the latter also sometimes referred to as perforin-like protein 1 (PLP1)) are siyiificant Plasmodium proteins that may play a role in cell traversal. See Yang et al., Cell Rep. 2017 Mar 28;18(13):3105-3116. doi: 10.1016 / j.celrep.2017.03.017, which is incorporated herein by reference in its entirety. Targeted disruption of P. falciparum SPECT1 or SPECT2 has been shown to reduce infectivity of sporozoites in liverstage development in humanized mice. However, mechanisms of cell traversal of these two proteins are yet to be defined in P. falciparum. See Yang et al.

[0356] SPECT1 and SPECT2 are considered attractive pre-erythrocytic immune targets due to the key role they are thought to play in the crossing of the malaria parasite across the dermis and the liver sinusoidal wall, prior toinvasion of hepatocytes. Recombinant P. falciparum SPECT2 has been shown to cause lysis of red blood cells in a Ca2-* -dependent manner, as has the MACPF / CDC domain of ASPECT2. ASPECT2 has also been implicated in the Ca2+ -dependent egress of P. falciparum merozoites from red blood cels.

[0357] SPECT1 and SPECT? sequences are known (see, e.g., UniProt accession numbers Q8IDR4 and Q9U0J9, each of which is incorporated herein by reference in its entirety), and exemplary amino add sequences for SPECT1 and SPEC!? are provided in Table 2.Exported Protein 1 (EXP 1

[0358] Exported protein 1 (EXP1) is a single pass transmembrane protein with an N-terminal signal peptide expressed during intraerythrocytlc stage and liver stage (see, e.g., Spielmann et al., Int J Med Microbiol. 2012 Oct;302(4-5): 179-86, which is Incorporated herein by reference In its entirety). EXP1 was shown to Initially localize to dense granules in merozoites and then be transported to parasltophorous vacuolar membrane (PVM) after invasion (see, e.g., Iriko et al., Parasitol Int. 2018 Oct;67(5):637-639, which is incorporated herein by reference in its entirety). Once localized to the PVM, EXP1 forms homo-oligomers with a N-terminus that is exposed to the parasltophorous vacuolar lumen and a C-terminus that is exposed to the red blood cell cytosol (see, e.g., Mesén- Ramrez et al., PLoS Biol. 2019 Sep 30;17(9):e3000473, which is Incorporated herein by reference in Its entirety).

[0359] EXP1 has been demonstrated to possess glutathione S-transferase (GST) activity that may protect Plasmodium from oxidative damage (see, e.g., Mesén-Ramirez et al., PLoS Biol 17(9) 2019 Sep 30;17(9):e3000473, which is incorporated herein by reference in its entirety). Recently, it was demonstrated that EXP1 is important for Plasmodium survival by maintaining correct localization of EXP2, a nutrient-permeable channel in the PVM (see, e.g., Mesen-Rami'rez et al., PLoS Biol. 2019 Sep 30;17(9):e3000473, which is Incorporated herein by reference in Its entirety).

[0360] P. falciparum EXP1 polypeptide sequences are known (see, e.g., UniProt accession number Q8IIF0,W7JTD3, Q25840, Q548U2, Q5VKK2, Q5VKK5, Q5WRH8, Q6V9G4, Q6V9G6, Q6V9G9, Q6V9H1, Q6V9H2, Q9U590, P04923, P04926, each of which is Incorporated herein by reference in its entirety). An exemplary EXP1 amino add sequence Is provided in Table 2.Unregulated In Infective Sporozoites Gene 3 (UIS3)

[0361] Upregulated in infective sporozoites gene 3 (UIS3) is a membrane-bouxi protein localized to sporozoite parasltophorous vacuolar membrane (PVM) in infected hepatocytes. UIS3 was shown to interact with liver fatty addbinding protein (L-FABP) and be involved in fatty acid and / or lipid import during phases of Plasmodium growth (see, e.g., Sharma et al., J Biol Chem. 2008 Aug 29; 283(35): 24077-24088; Mikolajczak et al., Int J Parasitol. 2007 Apr;37(5):483-9, each of which is incorporated herein by reference in its entirety).

[0362] After sporozoite invasion of host liver cells, there Is synthesis of vital Plasmodium structural features (e.g., parasltophorous vacuolar membrane). During hepatocytic stages, the Plasmodium relies on host fatty adds for rapid synthesis of its membranes (see, e.g., Sharma et al., J Biol Chem. 2008 Aug 29; 283(35): 24077-24088, which is incorporated herein by reference in its entirety). UIS3 insertion in the PVM provides Plasmodium a method to import essential fatty adds and / or lipids during rapid sporozoites growth phases (see, e.g., Sharma et al., J Biol Chem. 2008 Aug 29; 283(35): 24077-24088, which is incorporated herein by reference in its entirety).

[0363] Immunization with UIS3-defident Piasmodum berghei sporozoites protected against malaria in rodent malaria model (see, e.g., Mueller et al., Nature. 2005 Jan 13;433(7022): 164-7, which is incorporated herein by reference in its entirety). UIS3-defident Plasmodium berghei can start the transformation process in the liver;however, they show severe defects during transformation into trophozoites (see, e.g., Mueller et al., Nature. 2005 Jan 13;433(7022): 164-7, which is incorporated herein by reference in its entirety). UIS3-deficient Plasmodium berghei are also unable to develop into mature liver schizonts and therefore abort malaria infection within the liver itself (see, e.g., Mueller et al., Nature. 2005 Jan 13;433(7022): 164-7, which is incorporated herein by reference in its entirety). Further, it was previously demonstrated that UIS3 derived from Plasmodium berghei and UIS3 derived from Plasmodium faldparum exhibited a low (i.e. 34%) amino acid sequence identity (see, e.g., Mueller et al., Nature. 2005 Jan 13;433(7022): 164-7, which is incorporated herein by reference in its entirety).

[0364] Plasmodium UIS3 sequences are known (see, e.g., UniProt accession number A0A509ARS3, A0A1C6YLP3, Q8IEU1, A0A384KU1, A0A1G4H423, A0A077YB01, Q9NFU4, each of which is Incorporated herein by reference In Its entirety). An exemplary U1S3 amino acid sequence Is provided In Table 2.Early Transcribed Membrane Protein 10.3 (ETRAMP10.3) and Unregulated in Infective S es Gene 4 (UIS4)

[0365] Upregulated in infective sporozoites gene 4 (UIS4) contains a single transmembrane domain and localizes to secretory organelles of sporozoites and to the parasitophorous vacuole membrane (PVM) of liver stages. UIS4 is not expressed In blood stages or early sporozoites that are produced in oocysts (see, e.g., Mackellar et al., Eukaryot Cell. 2010 May; 9(5): 784-794, which is incorporated herein by reference in Its entirety).

[0366] Deletion of UIS4 gene is associated with arrest of early liver stage development (see, e.g., Vaughan and Kappe, Cold Spring Harb Perspect Med. 2017 Jun l;7(6):a025486, which Is Incorporated herein by reference in its entirety). Recently, UIS4 was demonstrated to be Involved in Plasmodium berghei survival by eluding host actin structures deployed as part of host cytosolic defense (see, e.g., Sana et al., (Science. 2022 Apr 22;25(5): 104281. doi: 10.1016 / j.isci.2022.104281. eCollection 2022 May 20, which Is Incorporated herein by reference In Its entirety). P. falciparum has an ortholog to UIS4 named ETRAMP10.3 which is not able serve as a functional compliment to P. yoeliiUIS4, Indicating It likely serves a different function In P. falciparum's lfie cycle (see Mackdlar et al., Eukaryot Cell 9:784-94 (2010), which is incorporated herein by reference In its entirety).

[0367] Plasmodium faldparum early transcribed membrane protein 10.3 (ETRAMP10.3) Is an approximately 10 kDa protein and member of the early transcribed membrane proteins multigene family, a family which is conserved across Plasmodium species and includes proteins located In the parasitophorous vacuole. Several ETRAMP proteins are specific to P. faldparum and not found In Plasmodium species that infect other organisms. ETRAMP10.3 is one example, which is expressed in both liver and blood stage P. faldparum parasites. ETRAMP10.3 transcription has been found to peak during the transition from ring to trophozoite stages of P. faldparum blood stage infection in a human host ETRAMP10.3 localizes to the parasitophorous vacuole and is exported to a host erythrocyte during blood stage infection. Although ETRAMP10.3 is sometimes referred to as Upregulated in Infectious Sporozoites gene 4 (UIS4), ETRAMP10.3 is understood to be an ortholog of UIS4 on the basis of synteny and structural similarity.However, ETRAMP10.3 is not a functional ortholog of UIS4 and may play a different biological role. Although the biological function of ETRAMP10.3 has not yet been completely resolved, localization to vesicular structures in the host erythrocyte suggests a role in host-parasite interaction or in remodeling of infected erythrocyte. ETRAMP10.3 appears to play a key role in the Plasmodium life cycle. When ETRAMP10.3 is deleted, the deletion can lead to the disruption of liver-stage development in mice and asexual blood stage progression.

[0368] Although the terms “UIS4" and "ETRAMP10.3” are in the literature sometimes used to refer to different proteins, in context of the present disclosure, the terms "UIS4* and "ETRAMP10.3" interchangeably to refer to ETRAMP10.3.

[0369] Plasmodium UIS4 sequences are known (see, e.g., UniProt accession number Q8DM9, which is incorporated herein by reference in its entirety). An exemplary UIS4 amino add sequence is provided in Table 2. Liver Specific Protein 1 fUSP-1)

[0370] Liver specific protein 1 (LISP-1) is expressed during Plasmodium development in hepatocytes and localized to the parasitophorous vacuolar membrane (PVM) (see, e.g., Ishino et al., Cell Microbiol. 2009 Sep; 11(9): 1329-1339, which is incorporated herein by reference in its entirety). LISP-1 was shown to be expressed at high levels during late liver stages development and to be involved in PVM breakdown and subsequent merozoite release (see, e.g., Ishino et al., Cell Microbiol. 2009 Sep; 11(9): 1329-1339, which is incorporated herein by reference in its entirety).

[0371] Intracellular Plasmodium deficient In LISP-1 develop into hepatic merozoites and display normal infectivity to erythrocytes (see, e.g., Ishino et al., Cell Microbiol. 2009 Sep; 11(9): 1329-1339, which is incorporated herein by reference in its entirety). However, USPl-defident liver-stage Plasmodium do not rupture PVM and remain trapped inside hepatocytes (see, e.g., Ishino et al., Cell Microbiol. 2009 Sep; 11(9): 1329-1339, which is incorporated hereto by reference in its entirety).

[0372] Plasmodium LISP-1 sequences are known (see, e.g., UniProt accession number A0A210C2X6, Q8ILR5, each of which is incorporated herein by reference in its entirety). An exemplary LISP-1 amino add sequence is provided In Table 2.Liver Specific Protein 2 fLISP-2)

[0373] Liver spedfic protein 2 (LISP-2) contains a modified 6-cys domain and is expressed during Plasmodium development in hepatocytes (see, e.g., Orito et al., Mol Microbiol. 2013 Jan;87(l):66-79, which is incorporated herein by reference In Its entirety). LISP-2 was shown to be expressed by liver stages Plasmodium, exported to hepatocytes, and be distributed throughout the host cell, including the nucleus (see, e.g., Orito et al., Mol Microbiol. 2013 Jan;87(l): 66-79, which is incorporated herein by reference In Its entirety).

[0374] Intracellular Plasmodium deficient in LISP2 do not mature effectively during merozoites development (see, e.g., Orito et al., Mol Microbiol. 2013 Jan;87(l):66-79, which is incorporated herein by reference In its entirety).

[0375] Plasmodium LISP-2 sequences are known (see, e.g., UniProt accession number A0A2I0BZR4, Q8I1X6, Q9U0D4, each of which is Incorporated hereto by reference in its entirety). An exemplary LISP-2 amino add sequence is provided in Table 2.Thrombosoondin-Related Adhesion Protein fTRAP)

[0376] Thrombospondin-related adhesion protein (TRAP) contains an N-terminal domain that is commonly referred to as von Willebrand factor A domain, although it is most similar to an integrin I domain because it contains a metal Ion-dependent adhesion site (MIDAS) with a bound Mg2tIon that Is required for sporozoite motility In vitro and infection in vivo (see, e.g., Lu et al., PLoS One. 2020; 15(1): e0216260, which is incorporated herein by reference in its entirety). The I domain is inserted in an extensible p-ribbon and followed by a thrombospondin repeat (TSR) domain, a proline-rich segment at the C-terminus, a single-pass transmembrane domain, and a cytoplasmic domain (see, e.g., Lu et al., PLoS One. 2020; 15(1): e0216260, which is incorporated herein by reference in its entirety). Sequence analysis of the proline-rich segment revealed the presence of SH3-domain binding PxxP motifs in PlasmodiumTRAPs (Akhouri et al., Malar J. 2008 Apr 22;7:63. doi: 10.1186 / 1475-2875-7-63, which is incorporated herein by reference in its entirety).

[0377] TRAP is stored in the mkronemes and becomes surface exposed at the sporozoite anterior tip when parasite comes in contact with host cells (Akhouri et al., Malar J. 2008 Apr 22;7:63. doi: 10.1186 / 1475-2875-7-63, which is incorporated herein by reference in its entirety). TRAP also plays an important role in liver cell invasion of sporozoites by helping sporozoites in gliding motility and in recognition of host receptors on the mosquito salivary gland and hepatocytes (Akhouri et al., Malar J. 2008 Apr 22;7:63. doi: 10.1186 / 1475-2875-7-63, which is incorporated hereto by reference in its entirety).

[0378] PlasmodiumTRAP sequences are known (see, e.g., UniProt accession numbers A0A5Q2EXK8, A0A5Q2EZD7, A0A5Q2F1F6, A0A5Q2F2B8, A0A5Q2F2H6, A0A5Q2F4G9, 076110, P16893, Q01507, Q26020, Q76NM2, W8VNB6, each of which is Incorporated herein by reference in its entirety), and an exemplary TRAP amino add sequence Is provided In Table 2.Liver-Staoe-Assodated Protein-1 (LSAP-1)

[0379] Liver-stage-associated protein (LSAP-1) has been shown to be found mainly at the periphery of the Intracellular hepatic parasite throughout its development, but not in blood stage parasites and possibly in minor quantities In salivary gland sporozoites (see, e.g., Siau et al., PLoS Pathog. 2008 Aug 8;4(8):el000121, which Is Incorporated herein by reference In Its entirety). LSAP-1 is among the most abundant transcripts In the salivary gland transcriptome but has not been detected in proteomlc surveys of sporozoites. Rather, expression has only been detected only In liver stages (see, e.g., Slau et al., PLoS Pathog. 2008 Aug 8;4(8):el000121, which is Incorporated herein by reference In its entirety).

[0380] Plasmodium LSAP-1 sequences are known (see, e.g., UniProt accession number Q8I632, W7JR53, each of which Is incorporated herein by reference in Its entirety). An exemplary LSAP-1 amino add sequence is provided In Table 2.Liver-Stage-! "Delated Protein-2 fLSAP-2)

[0381] Like LSAP-1, LSAP-2 Is also among the most abundant transcripts In the salivary gland transcriptome but has not been detected in proteomlc surveys of sporozoites. LSAP-2 has shown some efficacy as a vaccine when combined with other antigens. See, e.g., Halbroth et al., Infect Immun. 2020 Jan 22;88(2):e00573-19. doi: 10.1128 / IAI.00573-19. Print 2020 Jan 22, which Is incorporated herein by reference In its entirety.

[0382] Plasmodium LSAP-2 sequences are known (see, e.g., UniProt accession number Q8I632, W7JR53, each of which is incorporated herein by reference in its entirety). An exemplary LSAP-2 amino add sequence is provided in Table 2.Liver-Staae Antigen 1 (LSA-1)

[0383] Liver-Stage Antigen 1 (LSA-1) is expressed after Plasmodium have invaded hepatocytes and antigen accumulates in the parasitophorous vacuole (see, e.g., Tucker, K. et al., 2016, 'Pre-Erythrocytic Vaodne Candidates in Malaria', in A. J. Rodriguez-Morales (ed.), Current Topics in Malaria, IntechOpen, London. 10.5772 / 65592, each of which is incorporated herein by reference in its entirety). The function of LSA-1 remains currently not known (see, e.g., Tucker, K. et al., 2016, 'Pre-Erythrocytic Vacdne Candidates in Malaria', in A. J. Rodriguez-Morales (ed.), Cun-ent Topics in Malaria, IntechOpen, London. 10.5772 / 65592, which is incorporated herein by reference in its entirety).

[0384] LSA-1 is a 230 kDa preerythrocytic stage protein containing a large central region consisting of over eighty 17 amino add residue repeat units flanked by highly conserved C- and N-termlnal regions (Richie, T.L. and Parekh, F.K. (2009) Malaria, which is incorporated herein by reference in its entirety). In Vaccines for Biodefense andEmerging and Neglected Diseases (Barrett, A.D.T. and Stanberry L.R., eds), pp. 1309-1364, Elsevier, which is incorporated herein by reference in its entirety). LSA1 is expressed only by liver stage Plasmodium and not by sporozoites (Richie, T.L. and Parekh, F.K. (2009) Malaria, which is incorporated herein by reference in its entirety). In Vaccines for Biodefense and Emerging and Neglected Diseases (Barrett, A.D.T. and Stanberry L.R., eds), pp. 1309- 1364, Elsevier, which is incorporated herein by reference in its entirety). The repeat region results in significant variation of the protein between strains of Plasmodium falciparum (see, e.g., Tucker, K. et al., 2016, 'Pre-Erythrocytic Vaccine Candidates in Malaria', in A. J. Rodriguez-Morales (ed.), Current Topics in Malaria, IntechOpen, London. 10.5772 / 65592, which is incorporated herein by reference in its entirety).

[0385] Plasmodium LSA-1 sequences are known (see, e.g., UniProt accession number Q25886, Q25887, Q25893, Q26028, Q9GTX5, 096125, each of which Is Incorporated herein by reference In Its entirety). An exemplary LSA-1 amino acid sequence is provided in Table 2.Liver stage antigen 3 (LSA-3)

[0386] Liver stage antigen 3 (LSA-3) Is a 200-kDa protein that Is composed of three nonrepeating regions (NR- A, NR-B, and NR-C) flanking two short repeat regions and one long repeat region (see, e.g., Tucker, K. et al., 2016, 'Pre-Erythrocytic Vaccine Candidates in Malaria', in A. J. Rodriguez-Morales (ed.), which Is incorporated herein by reference in its entirety), Current Topics in Malaria, IntechOpen, London. 10.5772 / 65592, which is incorporated herein by reference in its entirety). The nonrepeat regions are well conserved across geographically diverse strains of Plasmodium faidparum (see, e.g., Tucker, K. et al., 2016, 'Pre-Erythrocytic Vaccine Candidates in Malaria', in A. J. Rodriguez-Morales (ed.), Current Topics In Malaria, IntechOpen, London. 10.5772 / 65592, which is Incorporated herein by reference in Its entirety). The most significant variation Is In the repeating regions due to organization and number of repeating subunits rather than composition of the repeating regions (see, e.g., Tucker, K. et al., 2016, 'Pre-Erythrocytic Vaccine Candidates In Malaria', in A. J. Rodriguez-Morales (ed.), Current Topics in Malaria, IntechOpen, London. 10.5772 / 65592, which is Incorporated herein by reference In its entirety).

[0387] Recently, in vitro data has shown that antibodies against LSA-3 (in particular, the C-termlnal portion of LSA-3) may provide some protection (see, e.g., Morita et al, Sci Rep. 2017 Apr 5;7:46086. doi: 10.1038 / srep46086, which is incorporated herein by reference in Its entirety).

[0388] Plasmodium LSA-3 sequences are known (see, e.g., UniProt accession number C7DU21, C7DU22, C7DU23, C7DU24, C7DU25, C7DU26, C7DU27, C7DU28, C7DU29, C7DU32, C7DU33, C7DU34, C7DU36, C7DU37, C7DU38, C7DU39, C7DU40, Q8I042, Q8I0A5, Q8I0D0, Q8IFR1, Q8IFR2, Q8IFR3, Q8IFR4, Q8IFR5, Q8IFR6, Q8IFR7, Q8IFR8, Q8IFR9, Q8IFS0, Q8IFS1, Q8IFS2, Q8IFS3, Q8IFS4, Q8IFS5, Q8IFS6, Q8IFS7, Q8IFS8, Q8IFS9, Q8IFT0, Q8IFT1, Q8IFT2, Q8IFT3, Q8IFT4, Q9U0N9, Q9U0P0, A0A2I0BVD6, A0PFM9, 096275, each of which is incorporated herein by reference In its entirety). An exemplary LSA-3 amino acid sequence is provided In Table 2.Glutamic Add-Rich Protein

[0389] Glutamic add-rich protein (GARP) is a 80kDA protein which derives its name from its glutamic rich amino add sequence which comprises 24% of all its residues. GARP Is predominantly expressed in ring stages and trophozoites and has been shown to be a non-essential gene in cell culture but highly immunogenic in animal models. Although GARP is non-essential in cell culture, its localization to the periphery of infected erythrocytes may indicate a role in the sequestration of infected erythrocytes. CARP'S involvement in sequestration has been proposed to occur by way of binding with an chloride / bicarbonate anion exchanger. Antibodies against GARP have been proposed to serve as signatures of protection against severe malaria and have shown efficacy in experimental trialsSEQ ID Protein Sequence (Amino Add) NO:7 CSP MMRKLAILSVSSFLFVEALFQEYQCYGSSSNTRVLNELNYDNAGTNLYNELEMNYYGKQE NWYSLKKNSRSLGENDDGNNEDNEKLRKPKHKKLKQPADGNPDPNANPNVDPNANPN VDPNANPNVDPNANPNANPNANPNANPNANPNANPNANPNANPNANPNANPNANPNA NPNANPNANPNANPNANPNANPNVDPNANPNANPNANPNANPNANPNANPNANPNAN PNANPNANPNANPNANPNANPNANPNANPNANPNANPNANPNKNNQGNGQGHNMPN DPNRNVDENANANSAVKNNNNEEPSDKH1KEYLNKIQNSLSTEWSPCSVTCGNGIQVRI KPGSANKPKDELDYANDIEKKICKMEKCSSVFNWNSSIGLIMVLSFLFLN8 TRAP MNHLGNVKYLVIVFUFFDLFLVNGRDVQNNIVDEIKYREEVCNDEVDLYLLMDCSGSIRR HNWVNHAVPLAMKUQQLNLNDNAIHLYASVFSNNAREIIRLHSDASKNKEKAUIIKSLL STNLPYGKTNLTDALLQVRKHLNDRINRENANQLWILTDGIPDSIQDSLKESRKLSDRG VKIAVFGIGQGINVAFNRFLVGCHPSDGKCNLYADSAWENVKNVIGPFMKAVCVEVEKTA SCGVWDEWSPCSVTCGKGTRSRKREILHEGCTSELQEQCEEERCLPKREPLDVPDEPED DQPRPRGDNFAVEKPNENIIDNNPQEPSPNPEEGKGENPNGFDLDENPENPPNPPNPPN PPNPPNPPNPDIPEQEPNIPEDSEKEVPSDVPKNPEDDREENFDIPKKPENKHDNQNNLP NDKSDRYIPYSPLSPKVLDNERKQSDPQSQDNNGNRHVPNSEDRETRPHGRNNENRSYPVlDLSQNNFQVNlYMHSKFlPNDYSLRKDIVPHmNNVPSNVFILSLKELLKTIFIQHME KSQTTTFQLNLYDFEVEFFILTFNRFTSKFHKMNSNVLSNLTISNFYSTYIHGGLFLNIDK1 KIDIPNLLNDFIDHFSKWIDFSHHNIVKQ _16 USP2 (3D7) MEKGSILSFIFFCSWIFIRFIGYFFCNRYMTEEPYNNIFBIKPENLYSSLLLLSNEKENDFP SSTNCNGYMKCIPFYNNVSERWKRYNFIQLYIIRSALNIHVMSKYNMLNKYNKETMRLLK RNNNVENRINNISNHYLCSGFKKENRLFFI±FYIG1KMMKLYIRNLFMKYIKIYYKTKHFEK NIETMKKWYVERDNLFDIERNNLFDILYMLKRIDSYVKNIYSIISNNFLYVIRIIFLPFEKIY FSLKSUMIKKMNMSSSYYYYYVNMFSLYKKNYNKYEEIFIHEQRVIYPNEYLKNEMLDKY RRVIRILSGQHDNPFIDSLLINPEKIEKDDLDVKQKKKKIIEELKKKKENTNTNTNTSTNTS ANTNTSTNTSANTNTSTKESHILDESKLETFYRDELDKMGKEBETYFKGNIDKKSLDEFH KILLEELNKMDKDELYEMYREELNRIEQEKIRNMNKEEINKTYKDBNNMNSDQVDKIHR EELEK1EKEKINKMDKDEIDKIYREELDKMDRDAIYSMYIEDISNKN1KDL1KNEKETNKDK NKKKDIDINKKKKKDIDIDVDIDKDIHKDHVEELYGEVKNKLSKEELDRMDRDALYRVYL EELDRMNRDELYRVYLEELEKIDKEEKEKIHREKLHKIEKEKINKMDKDQIDKIYEEELNK MDSDEIQHVRRAILQDIQKEKIQNLELEBDRLYKEELDRMDREARYEIPMRNLSRNEKD NIIHRNIKNESNQKNKKENVNVFIIHDNNDSNNNNNNNNRDVNNLNNKHTNNNYNENV EVELWRNLDKDKGAKIEDIIDYFNKEIKKDKNVNVSNIVNFLNSKVGKDNTPIQHKKEN QVDWRKNIQIIQEDNIKNKGQKDNTEMLDNNKEITNID1KNVDDIKNVGDIKSVGDIKS VDDINNVDGIKNVDGIKNVDGIKNVDGINNVGDINNAGDTNNAGDINNVGDINNSVDIY NVEHIDEAEKKPNLDNPKKFDWTQVFKDKVTEKIKNEEKFNNSKENIQNDIRDKEIHKD DRIKGITSREKNAEEINNNEKKDKFVYEFYTSNKKENIDKEEENNIDDKNIKIEIEPNYEIN NNFEEENKNEINVIIDKEAKNNMDKDDSNNNNNIQKNNIIIKDNTNVSEEVHITESSKEIA EFFNNIIKNSNILDMCSKMNASDSEKGFICINGNNYIINPGTYHIINIKYPDYNNVRKKWY DSMDCISINNKDENNNNKEHNYYNKNDDDLYLKKSVEEFIPGFLSNINKVDDLARIFTPS FIQNDIFLNCIYKYRNDFDKNNNIYSFPMK1FLRKNSTKIKGCSFQIDEDPLLYKDYSEKES FLSNKIILNNSNRNTECVLHASNEIVGFQCGPPYKSYDNIQYRHLTNKSNDIQKNIFGIYS NNNSSYSHLFKNIFNNEHKLYNVGGYFQTEPINCFEFVNDNINVEDILPGAVPFPRFDLIH HDLDVNQTRYILLNETNQDKTISCTCNYFTEPNIVYTGKIIIKVEEEKIYICrKKLQTEFNDI INNKKEIYHEKKMNHIIKEKKDEDENDMSFNKNYVNNYNENFKINDINNFYNRNNHPNN NYHNDYHNNHSSKGNHTNKIHDTFLKNKYNISFNNLKFYNIKHENKNNQDVINYEYNVD DYHEVQDGQDESFKEEEDFJDFKENIINDNTNHNNTDLDDDKYNKYHNNNNNNNNNSS FKSIESNLDLQRSILQSGDTQQVWINKSKNVNVLFPDKKKNHTHPNEEKRTFPKYISLVY KEKNKDNEKIDICTLTHKEFYPPLLRGGKDSDPENKQTGVEINNGVEKKNDVQIKNDVEI KNDVEIKNDVBNDDVEIKNDVE1KNDVBKNDVEINDDVBNDDVEINNGVEINDGVEN KDN1HEGNNNLENDSFNEDT1EEPFENIFDFINEETSSNENSBILDSADSIKRKLGHNFLD IISAGKFKIRHKEKKTKNKKKK _17 EXP1 (3D7) MKJLSVFFLALFHIFNKESLAEKTNKGTCSGVSSKKKNKKGSGEPUDVHDUSDMIKKEE ELVEVNKRKSKYKLATSVLAGLLGWSTVLLGGVGLVLYNTEKGRHPFKIGSSDPADNANP DADSESNGEPNAGPQVTAQDVTPEQPQGDDNNLVSGTEH _18 EXP2 (3D7) MKVSYIFSFFLLFFVYKNTNTWCDNGYGDLAATSALTTVIKDPISLTIKDIYEHGVKNPFT KIIHKLKKHRYRKVLRWSRMWWVLLVREIVGDNnEKKTEKALREIWDQCnAVYNNTL NAVESKPLLFLHGILNECRNNFATKLRQDPSUVAKIDQIIKSQIYRFWVSEPYLKIGRSHT LYTHrrPDAVPQLPKECTlKHLSSYMEEKLKSMESKKNIESGKYEFDVDSSETDSTKDDG KPDDDDDDDDNFDDDDNFDDDTVEEEDASGDLFKNEKKDENKE _19 SPELD (3D7) MCSTYSVEPLVYDSYEYVYLKPKKAGTSAVYYPLNISWKYVAKKRSVGCFGSRKKYTLIP EAYYYPYYYYYVYYYPSAARLVRTTKKEKVLKENNNKESEDENKQDNVGTEKKECDCSEK EKYIPTYVPLTESYYFPPSALYVPHYSVLVP _20 PL (3D7) MSSILLFFWFQYLUSFSGT5YKRFWDGASIFLRNPYKITLGKSEKKGKVFSEFSEEEDSI VRRDTEKKKKWFGKGNDVNKKVKEKKNVILEEKQIGKEENNLVGQQNDSVGQQNDSVG QQNOSVGQQNDPVGQQNDSVGQQNDPVGQQNDPVGQQNDYVGQQNDSVGQQNDY VGQQNDYVGQQNDPVGQQNDSVGQQNDYVGQQNDPVGQQNDPVGQQNDPVGQQN DSVGQQNDYVGQQNDPVGQQNDYVGQQNDYVGQQNDPVGQQNDPVGQQNDPVEQ EDNVGIVKKEKKEKIIVEKENEIGVIERENISGVEV1NKDSEEDIYNSNVDKNFPADDNNR DBLVRRKKVSNKDSLFMNDIIRGENEDNDDDNEEEEEKVSKNLENVKLGELSKLQYIFG TNHDNDDDSEIRSESBDDIDELDEEEYDWTEHVYNYKPTTYLLPGLGGSTLIAEYKNAT IHSCSRYLLNSKPFRIWISLSRLLSlQSNIYCTFDTIRLKYDEKKNIYYNQPGVnDVEKFG NLKGIEYLDYFNNTGIGITKYFNWGQYFTSHGYVDGESIIGAPYDWRYPLSQQNYKILKE HIEYIYEKRNGTKVNUGHSLGGLYLNFFLSRWSKKWKQKHLSKIIFISTPFKGSVKnRA UQSRKDnSFRJTKLIKLSIPESMMKALGNSLGSLFDILPYREYYKRDQVVIUNMSNTPIDEDHVQYLVRCGIYKPECYRNRADVNLKVYTLKNWHELLDDKLKAKYENYKLYRERYYNK DHGVPrYCLYSmNKKETEYLLYFETQNTREEPTIYYGTGDGnrVGTESLQACSNFYNTVLT HHFSDTSHVGILYTMETAKYIYDIVESPN _21 E140 MVDFNDLSVELKKTEUKEDLRNLSHIINNEFSYFCQNENKNVSFNNNISSYYNDDIFSKS TLNNLYTSWKLEDFSHFDFSSILDILKRNQYVMCSIYFLLIFSCIYFLTLLLYTKCIKTTLKK WFCRYCSENINENNSNHNEQRTVLQNVINKSCYFITYSSIICLLLFLLLSGITYMHYFIKTK KGIHSNICNIYTRLDKFLLNKCLDPKKVDTSCYSAEHILNDLSSILEEYKKVKQQAKDDTLL DENTPFPLLERYnTFNKLNVLKNNINKNNTTLENEYFHTYPALKGISETLTTIISEGNKNF GNARNVIKEVKSTIKYSFHTVDETIRNVFKDSVPKlTGLrTQAGKSIKGINNKYKIKERlPK YTNIILLTNIILLLPPFLILLGIIIFMIFILMGYIQKNNNFFIKLFGHFSAYFGLLTIIILSFGILFL STSVIGGTSCILSERILKNELRFDILNNTLIDYCIKNESAPLIDDDITTSFVAKINSFDTGHI DHNINEYEKHFTILKESFFHKSLKFMDYIWIVIMKRENNTFLNRIRTEQVKKSLIJTGIINE NIKYENMEAIGIRSYLTTLNKIIFPENNGKICFNDIICEKENNTYNnENSiarTDQKYRNIR DGMDEHLRNDLDAIVQLFVYKARILKENIFDINDLDSNEKNKIGWSEYTPRNINGTQKKS IINTFLVNVIESINFSEIINFFDKMRDQFNVLKDULLKIDTLTENTKCNKLVKELINVRKDY CNNVVLNLSTLSVYUIFSrrSFLLWYLFLFLWFYYNIKPS _22 AMA1 MRKLYCVLLLSAFEFTYMINFGRGQNYWEHPYQNSDVYRPINEHREHPKEYEYPLHQEH TYQQEDSGEDENTLQHAYPIDHEGAEPAPQEQNLFSSIEIVERSNYMGNPWTEYMAKYD IEEVHGSGIRVDLGEDAEVAGTQYRLPSGKCPVFGKGIIIENSNTTFLTPVATGNQYLKDG GFAFPPTEPLMSPMTLDEMRHFYKDNKYVKNLDELTLCSRHAGNMIPDNDKNSNYKYPA VYDDKDKKCHILYIAAQENNGPRYCNKDESKRNSMFCFRPAKDISFQNYTYLSKNWDN WEKVCPRKNLQNAKFGLWVDGNCEDIPHVNEFPAIDLFECNKLVFELSASDQPKQYEQH LTDYEKIKEGFKNKNASMIKSAFLPTGAFKADRYKSHGKGYNVVGNYNTETQKCEIFNVKP TCLINNSSYIATTALSHPIEVENNFPCSLYKDEIMKEIERESKRIKLNDNDDEGNKKIIAPRI FISDDKDSLKCPCDPEMVSNSTCRFFVCKCVERRAEVTSNNEVWKEEYKDEYADIPEHK PTYDKMKIIIASSAAVAVLATILMVYLYKRKGNAEKYDKMDEPQDYGKSNSRNDEMLDPE ASFWGEEKRASHTTPVLMEKPYY _23 GARP MNVLFLSYNICILFFWCTLNFSTKCFSNGLLKNQNILNKSFDSITGRLLJNETELEKNKDDN SKSERLKEEKDEKDDVPTTSNDNLKNAHNNNEISSSTDPTNIINVNDKDNENSVDKKKD KKEKKHKKDKKEKKEKKDKKEKKDKKEKKHKKEKKHKKDKKKEENSEVMSLYKTGQHKP KNATEHGEENLYEEMVSEINNNAQGGLLLSSPYQYREQGGCGIISSVHETSNDTKDNDK ENISEDKKEDHQQEEMLKTLDKKERKQKEKEMKEQEKIEKKKKKQEEKEKKKQEKERKK QEKKERKQKEKEMKKQKKIEKERKKKEEKEKKKKKHDKENEETMQQPDQrSEETNNEIM VPLPSPLTDVTTPEEHKEGEHKEEEHKEGEHKEGEHKEEEHKEEEHKKEEHKSKEHKSKG KKDKGKKDKGKHKKAKKEKVKKHWKNVIEDEDKDGVEIINLEDKEACEEQHrTVESRPL SQPQCKLIDEPEQLTLMDKSKVEEKNLSIQEQLIGTIGRVNWPRRDNHKKKMAiaEEAEL QKQKHVDKEEDKKEESKEVEEESKEVQEDEEEVEEDEEEEEEEEEEEEEEEEEEEEEEDEV EEDEDDAEEDEDDAEEDEDDAEEDDDDAEEDDDDAEEDDDEDEDEDEEEEEDEEEEEE SEKKIKRNLRKNAKI _24 PIESP2 MLLFFAKLWFTFFFWLLKYGKTRSYPKSGHKGHTKLNQPWRTLADFNDMFANQKNTF NFLKHINHYKNEQDTNNTHTPNHDEYSHNLPKNHEESNANMNNHNSFNDKSVNKKEAF DQFLQTLLNNYEIMHKEDESKESNQHNYKEGPSYEDKKNMYKEILKGYYNVFFENYAND TESNVHNKPEEVHKHEEIHKHRKLHKHEEVHKPEEFHKPEEFHKHEKVHKHEEVHKPEEV HKHEENHKHEENHKPQMVGQAPPEKEIRQESRTULGSFPQAGBLREDLWNKEDNKFS YALDPNDYASIEDKLLGSIFGYFKKNHDNLVKHLLQQIHTYKHKYMELKEQYINEVMKLK KIYNKSIMVIFIASCISILGPVMLHMHQNNPEEFFATILSFSISLGLHNLLLT _25 SEA-l / SEP-1 MMENKYPNELFCYINRYNINEIIENGEEKYVNEYDEDKNMSINHMNENDGICEYEIPFLL DYVDDSNKEDSEKNSLKSYLDDGASULSKPDELENYNKQNENEFDENNNNKNNKIDQL KEKINIIIIPNKGVINNFEEILSMANRNDKNIEKKLNDRFYQICCKSIADINTHNLNKIKDLK KKKNNKGSLNIEHlDYGDlFLTIHDnKSNNKIKGNNKTNLLHDSSYEIKKKTRRGTNIYK NPFHHRGSYLTSYENQKDIIYLNNLNNIMMDKYSNCSDSRKKEYSHFNSQEFSYDKYSM KDRMFLKNLYMKQNRLRDKRGKYHKLGDYQNIENYRKTGEHSFDCMNMSDIMHSNKM SHVNIMDHM1YKDNNNMSKLVDTINSREKDVKNYDDNFESYNNFFKNNNDEQHICLEY DDTYNLKDTVKNIIVEEEQCGKGVAaCDKNEDVDDLFVSKKTNYSSNKKREDYEKVFLE DNLHLKQTPSKRTKINIIPDYYDNNRSNKSYKENEEDALFEVCGSLKNDDILYKDNKLNVI NEDNIKEEDDKESWHLDNDEDKKEEMYKDVYPNVLSCEKEnRRNEKYNKSLNSTSSFE KIDNPSEINVESKEDTEYFDLUKKYEDTKINVYDNESLLLDLSNELREEMAKGDSNKNVN KVEDNDNKKENICHDNIMEDICHNNNVEDMYRNNNVEDMYRNNNVEDMYRNNNVED MYRNNNVEDVCHNNNVEDVCHNNNVEDVCHNNNVEDVYHNNNVEDMYHDNNIEDVCn. Piasmodium polypeptide constructs

[0392] The present disclosure, among other things, utilizes RNA technologies as a modality to express one or more Plasmodium polypeptide construct that includes one or more malarial proteins, or one or more portions thereof, described herein. For example, In some embodiments, a Plasmodium polypeptide construct comprises one or more Plasmodium Rh5 invasion complex polypeptides or portions thereof (e.g., antigenic portions of one or more Plasmodium Rh5 Invasion complex polypeptides). In some embodiments, one or more polypeptides or portions thereof of a Plasmodium Rh5 invasion complex can Include one or more polypeptides or portions thereof of a Plasmodium reticulocyte-binding protein homolog 5 (Rh5), a Plasmodium Cysteine-Rjch Protective Antigen (CyRPA), a Plasmodium Rh5-lnteracting Protein (Rlpr), a Plasmodium P 113, a Plasmodium thrombospondin-related apical merozoite protein (TRAMP), and / or a Plasmodium cysteine-rich small secreted protein (CSS). In some embodiments, a portion of a Rh5 invasion complex polypeptide can be a characteristic portion of a Rh5 invasion complex polypeptide. In some embodiments, a Plasmodium polypeptide construct additionally Includes one or more additional amino acid sequences, such as a secretory signal (e.g., a heterologous secretory signal), a transmembrane region (e.g., a heterologous transmembrane region), a multimerization region, and / or a linker, as described herein.A. Certain Plasmodium RhS Invasion Complex Polypeptides or Portions Thereof1. RhS

[0393] In some embodiments, a Plasmodium polypeptide construct described herein includes one or more Plasmodium Rh5 invasion complex polypeptides or portions thereof (e.g., antigenic portions thereof) that comprise one or more Plasmodium reticulocyte-binding protein homolog 5 (Rh5) polypeptides or antigenic portions thereof.

[0394] In some embodiments, a Plasmodium polypeptide construct described herein includes one or more polypeptides or antigenic portions of an Rh5 polypeptide, e.g., Plasmodium Rh5 polypeptide, e.g., P. fafciparum Rh5 (SEQ ID NO: 1), or a variant thereof (e.g., a glycosylation variant). In some embodiments, an Rh5 polypeptide may include a Plasmodium Rh5 N-terminal disordered domain, a first Plasmodium Rh5 ordered domain, a Plasmodium Rh5 linking disordered domain, a second Plasmodium Rh5 ordered domain (e.g., a C-terminal Plasmodium Rh5 ordered domain), or a combination thereof. A portion of Rh5 (or Rh5 polypeptide portion) (e.g., an antigenic portion of Rh5 or Rh5 antigenic portion) may refer to parts of an Rh5 polypeptide domain or parts spanning two or more Rh5 polypeptide domains.

[0395] In some embodiments, a Plasmodium polypeptide construct comprises one or more antigenic portions of Rh5. In some embodiments, one or more antigenic portions of Rh5 comprise one or more Rh5 ordered domains. In some embodiments, a Plasmodium Rh5 polypeptide or antigenic portion thereof comprises 25, 30, 35, 40, or 45 contiguous amino adds of an Rh5 ordered domain, or a variant thereof (e.g., a glycosylation variant).

[0396] In some embodiments, a Plasmodium Rh5 antigenic portion comprises an Rh5 ordered domain that corresponds to amino adds 140-247 or amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) or variants thereof (e.g., glycosylation variants). In some embodiments, a Plasmodium Rh5 antigenic portion comprises an Rh5 ordered domain that corresponds to amino acids 297-526 of a wild-type Rh5 sequence (SEQ ID NO: 1), or a variant thereof (e.g., a glycosylation variant). In some embodiments, one or more antigenic portions of Rh5 comprise (i) an Rh5 ordered domain that corresponds to amino adds 140-247 or amino acids 146-247 of a wild-type Rh5 (SEQ ID NO: 1) or variants thereof and / or (ii) an Rh5 ordered domain that corresponds to amino adds 297-526 of a wild-type Rh5 sequence (SEQ ID NO: 1), or a variant thereof.

[0397] 140-247 Ordered Domain of RhS (SEQ ID NO. 118)KNVNFLQYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKCIAVDAFIKKINETYDKVKSKCNDIKN DLIATIKKLEHPYDINNK

[0398] 146-247 Ordered Domain of RhS APMX (SEQ ID NO. 119)QYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKCIAVDAFIKKINETYDKVKSKCNDIKNDLIATIK KLEHPYDINNK

[0399] 297-526 Ordered Domain of RhS (SEQ ID NO. 120)NRTFKKMMDEYNTKKKKLIKCIKNHENDFNKICMDMKNYGTNLFEQLSCYNNNFCNTNGIRYHYDEYIHKLILSVKSKNLNKDLSDM TNILQQSELLLTNLNKKMGSYIYIDTIKFIHKEMKHIFNRIEYHTKIINDKTKIIQDKIKLNIWRTFQKDELLKRILDMSNEYSLFrTSDH LRQMLYNTFYSKEKHLNNIFHHL1YVLQMKFNDVPIKMEYFQTYKKNKPLTQ

[0400] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise one or more unpaired cysteines. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise two unpaired cysteines, in some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a cysteine at position 203, 329, or both, as numbered according to SEQ JD NO: 1. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise a tyrosine at position 203, 329, or both, as numbered according to SEQ ID NO: 1.

[0401] 140-247 Ordered Domain of RhS - C203Y (SEQ ID NO. 121)KNVNFLQYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKYIAVDAFIKKINETYDKVKSKCNDIKN DLIATIKKLEHPYDINNK

[0402] 146-247 Ordered Domain of Rh5 APMX - C203Y (SEQ ID NO. 122)QYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKYIAVDAFIKKINETYDKVKSKCNDIKNDLIATIK KLEHPYDINNK

[0403] 297-526 Ordered Domain of Rh5 - C329Y (SEQ ID NO. 123)NRTFKKMMDEYNTKKKKLIKCIKNHENDFNKIYMDMKNYGTNLFEQLSCYNNNFCNTNGIRYHYDEYIHKULSVKSKNLNKDLSDMTNILQQSELLLTNLNKKMGSYIYIDTIKFIHKEMKHIFNRIEYHTKIINDKTKIIQDKIKLNIWRTFQKDELLKRILDMSNEYSLFITSDHLRQMLYNTFYSKEKHLNNIFHHUYVLQMKFNDVPIKMEYFQTYKKNKPLTQ

[0404] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise one, two, three, or four N-linked glycosylation sites. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise two N-linked glycosylation sites. In some embodiments, one or more Plasmodium Rh5 antigenic portions comprisean amino acid substitution at one or more N-linked glycosylation sites, where the amino add substitution prevents glycosylation. In some embodiments, an amino acid substitution that prevents glycosylation comprises a NX[T / S] to QX[T / S] substitution. In some embodiments, amino acid substitution prevents glycosylation comprises a NX[T / S] to NXA substitution. In some embodiments, one or more Piasmocfium Rh5 antigenic portions comprise an amino add substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0405] In some embodiments, a Piasmodkim Rh5 antigenic portion comprises a Rh5 ordered domain that corresponds to amino adds 140-247 of a wild-type Rh5 (SEQ ID NO: 1) (or amino adds 140-247 of SEQ ID NO: 1 having 1, 2, 3, 4, or 5 amino add substitutions). In some embodiments, an Rh5 ordered domain corresponds to amino acids 140-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a cysteine at position 203. In some embodiments, an Rh5 ordered domain corresponds to amino adds 140-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a tyrosine at position 203. In some embodiments, an Rh5 ordered domain corresponds to amino adds 140-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises an N linked glycosylation site at N214. In some embodiments, an Rh5 ordered domain corresponds to amino adds 140-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises an amino add substitution that prevents glycosylation at position 214. In some embodiments, an amino add substitution that prevents glycosylation at position 214 comprises a NX[T / S] to QX[T / S] substitution. In some embodiments, amino add substitution prevents glycosylation at position 214 comprises a NX[T / S] to NXA substitution.

[0406] 140-247 Ordered Domain of RhS - N214Q (SEQ ID NO: 124)KNVNFLQYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKCIAVDAFIKKIQETYDKVKSKCNDIKNDUATIKKLEHPYDINNK

[0407] In some embodiments, a Rh5 ordered domain corresponds to amino adds 140-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a tyrosine at position 203 and glutamine at position 214.

[0408] 140-247 Ordered Domain of RhS - C203Y - N214Q (SEQ ID NO: 125)KNVNFLQYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKYIAVDAFIKKIQETYDKVKSKCNDIKNDUATIKKLEHPYDINNK

[0409] In some embodiments, an Rh5 antigenic portion (e.g., a Rh5 ordered domain) comprises a Plasmepsin X (PMX) deavage site. PMX is a conserved aspartic protease that is responsible for proteolytic processing and activation of proteins and other proteases involved in life cyde progression and / or development of Plasmodium.

[0410] In some embodiments, a PMX cleavage site of an Rh5 ordered domain comprises a sequence of FLQY (SEQ ID NO: 36), where cleavage occurs between L and Q. In some embodiments, a cleaved Rh5 ordered domain corresponds to amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) or a variant thereof.In some embodiments, an Rh5 antigenic portion (e.g., an Rh5 ordered domain) does not comprise a Plasmepsin X (PMX) deavage site.

[0411] In some embodiments, a Plasmodium Rh5 antigenic portion comprises a Rh5 ordered domain that corresponds to amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) (or amino adds 146-247 of SEQ ID NO: 1 having 1, 2, 3, 4, or 5 amino add substitutions). In some embodiments, an Rh5 ordered domain corresponds to amino acids 146-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a cysteine at position 203. In some embodiments, an Rh5 ordered domain corresponds to amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a tyrosine at position 203. In some embodiments, an Rh5 ordered domain corresponds to amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises an N linked glycosylation site at N214. In someembodiments, an Rh5 ordered domain corresponds to amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises an amino add substitution that prevents glycosylation at position 214. In some embodiments, an amino add substitution that prevents glycosylation at position 214 comprises a NX[T / S] to QX[T / S] substitution. In some embodiments, amino add substitution prevents glycosylation at position 214 comprises a NX[T / S] to NXA substitution.

[0412] 146-247 Ordered Domain of RhS APMX - N214Q (SEQ ID NO: 126)QYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKCIAVDAFIKKIQETYDKVKSKCNDIKNDLIATIK KLEHPYDINNK

[0413] In some embodiments, an Rh5 ordered domain corresponds to amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a tyrosine at position 203 and glutamine at position 214.

[0414] 146-247 Ordered Domain of RhS APMX - C203Y - N214Q (SEQ ID NO: 127)QYHFKELSNYNIANSIDILQEKEGHLDFVIIPHYTFLDYYKHLSYNSIYHKSSTYGKYIAVDAFIKKIQETYDKVKSKCNDIKNDLIATIK KLEHPYDINNK

[0417] 297-526 Ordered Domain of RhS N297Q (SEQ ID NO. 128)QRTFKKMMDEYNTKKKKLIKCIKNHENDFNKICMDMKNYGTNLFEQLSCYNNNFCNTNGIRYHYDEYIHKLILSVKSKNLNKDLSDM TNILQQSELLLTNLNKKMGSYIYIDTIKFIHKEMKHIFNRIEYHTKIINDKTKIIQDKIKLNIWRTFQKDELLKRILDMSNEYSLFITSDH LRQMLYNTFYSKEKHLNNIFHHUYVLQMKFNDVPIKMEYFQTYKKNKPLTQ

[0418] In some embodiments, an Rh5 ordered domain corresponds to amino adds 297-526 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a tyrosine at position 329 and / or glutamine at position 297.

[0419] In some embodiments, an Rh5 ordered domain corresponds to amino adds 297-526 of a wild-type Rh5 (SEQ ID NO: 1) and conyrises a cysteine at position 329 and asparagine at position 297.

[0420] 297-526 Ordered Domain of RhS - N297Q - C329Y (SEQ ID NO: 129)QRTFKKMMDEYNTKKKKLIKQKNHENDFNKIYMDMKNYGTNLFEQLSCYNNNFCNTNGIRYHYDEYIHKLILSVKSKNLNKDLSDM TNILQQSELLLTNLNKKMGSYIYIDTIKFIHKEMKHIFNRIEYHTKHNDKTKIIQDKIKLNIWRTFQKDELLKRILDMSNEYSLFITSDH LRQMLYNTFYSKEKHLNNIFHHUYVLQMKFNDVPIKMEYFQTYKKNKPLTQ

[0421] In some embodiments, a Plasmodium Rh5 polypeptide or antigenic portion thereof comprises an Rh5 disordered domain or antigenic portion thereof. In some embodiments, an Rh5 disordered domain is an Rh5 N- terminal disordered domain that corresponds to amino adds 26-139 of a wild-type Rh5 (SEQ ID NO: 1). In someembodiments, an Rh5 disordered domain is an Rh5 linking disordered domain that corresponds to amino adds 248- 296 of a wild-type Rh5 (SEQ ID NO: 1).

[0422] 26-139 Disordered Domain of RhS (SEQ ID NO: 130)ENAIKKTKNQENNLTLLPIKSrEEEKDDIKNGKDIKKBDNDKENIKTNNAKDHSTYIKSYLNTNVNDGI-KYLFIPSHNSFIKKYSVFN QINDGMLLNEKNDVKNNEDYKNVDY

[0423] 248-296 Disordered Domain of RhS (SEQ ID NO: 131)NDDSYRYDISEHDDKSEETDDETEEVEDSIQDTDSNHTPSNKKKNDLM

[0424] In some embodiments, one or more Plasmodium Rh5 antigenic portions comprise two Rh5 ordered domains and one Rh5 disordered domain. In some embodiments, one or more Plasmodium Rh5 antigenic portions correspond to amino adds 140-526 of a wild-type Rh5 (SEQ ID NO: 1). In some embodiments, one or more Piasmocfium Rh5 antigenic portions correspond to amino adds 26-247 and 297-526 of a wild-type Rh5 (SEQ ID NO: 1).

[0425] In some embodiments, a Plasmodium polypeptide construct does not include an Rh5 disordered domain. In some embodiments, a Plasmodium Rh5 polypeptide or antigenic portion thereof does not comprise an Rh5 disordered domain that corresponds to amino adds 26-139 or amino acids 248-296 of a wiki-type Rh5 (SEQ ID NO: 1).In some embodiments, a Plasmodium polypeptide construct does not Indude an Rh5 secretory signal, e.g., does not indude a sequence corresponding to amino adds 1-25 of a wild-type Rh5 (SEQ ID NO: 1).

[0426] RhS secretory signal (SEQ ID NO: 132)MIRIKKKULTIIYIHLFILNRLSF

[0427] In some embodiments, a Plasmodium polypeptide construct comprises one or more Plasmodium Rh5 polypeptides or antigenic portions thereof comprising two Rh5 ordered domains. In some embodiments, a Plasmodium polypeptide construct comprises two Plasmodium Rh5 antigenic portions, where each antigenic portion comprises an Rh5 ordered domain. In some embodiments, a Plasmodium polypeptide construct comprises two Rh5 ordered domains that correspond to (I) amino adds 140-247 or 146-247 of a wild-type Rh5 (SEQ ID NO: 1) or variants thereof and (II) amino adds 297-526 of a wild-type Rh5 (SEQ ID NO: 1) or variants thereof. In some embodiments, a Plasmodium polypeptide construct comprises two Rh5 ordered domains that are directly adjacent to one another.

[0428] In some embodiments, a Plasmodium polypeptide construct comprises an Rh5 polypeptide comprising exactly two antigenic portions of Rh5, where the two antigenic portions comprise or consist of two Rh5 ordered domains. In some embodiments, two Rh5 ordered domains correspond to (i) amino acids 140-247 or amino adds 146-247 of a wild-type Rh5 (SEQ ID NO: 1) or variants thereof and (II) amino acids 297-526 of a wild-type Rh5 (SEQ ID NO: 1) or variants thereof.

[0429] In some embodiments, a Plasmodium polypeptide construct comprising two Rh5 ordered domains, where a first Rh5 ordered domain corresponds to amino adds 140-247 or amino acids 146-247 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a tyrosine at position 203 and glutamine at position 214, and where a second Rh5 ordered domain corresponds to amino adds 297-526 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a tyrosine at position 329 and / or glutamine at position 297.

[0430] In some embodiments, a Plasmodium polypeptide construct comprising two Rh5 ordered domains, where a first Rh5 ordered domain corresponds to amino acids 140-247 or amino acids 146-247 of a wild-type Rh5(SEQ ID NO: 1) and comprises a tyrosine at position 203 and glutamine at position 214, and where a second Rh5 ordered domain corresponds to amino adds 297-526 of a wild-type Rh5 (SEQ ID NO: 1) and comprises a cysteine at position 329 and asparagine at position 297.

[0431] In some embodiments, a Plasmodium polypeptide construct does not include a Rh5 disordered domain (e.g., does not indude amino adds 26-139 or amino adds 248-296 of a wild-type Rh5 (SEQ ID NO: 1). In some embodiments, a Plasmodium polypeptide construct does not include a Rh5 secretory signal, e.g., does not indude a sequence corresponding to amino adds 1-25 of a wild-type Rh5 (SEQ ID NO: 1).

[0432] In some embodiments, a Plasmodium polypeptide construct comprises one or more antigenic portions of Plasmodium Rh5 comprising a PMX deavage site. In some embodiments, a Plasmodium polypeptide construct comprises one or more antigenic portions of Plasmodium Rh5 comprising a PMX cleavage site that comprises or consists of an amino add sequence of NFLQ (SEQ ID NO: 189).2. CyRPA

[0433] In some embodiments, a Plasmodium polypeptide construct described herein Includes one or more Plasmodium Rh5 invasion complex polypeptides or portions thereof (e.g., antigenic portions thereof) that comprise one or more Plasmodium Cysteine-Rich Protective Antigen (CyRPA) polypeptides or antigenic portions thereof.

[0434] In some embodiments, a Plasmodium polypeptide construct described herein includes one or more regions or portions (e.g., antigenic portions) of a CyRPA, e.g., Plasmodium CyRPA, e.g., P. falciparum CyRPA (SEQ ID NO: 3), or a variant thereof (e.g., one or more antigenic portions of a CyRPA, e.g., Plasmodium CyRPA, e.g., P. falciparum CyRPA).

[0435] In some embodiments, a Plasmodium polypeptide construct comprises an antigenic portion of CyRPA. In some embodiments, a Plasmodium CyRPA polypeptide or antigenic portion thereof comprises 25, 30, 35, 40, or 45 contiguous amino adds of CyRPA, or a variant thereof (e.g., a glycosylation variant).

[0436] In some embodiments, a Plasmodium CyRPA antigenic portion does not comprise an endogenous signal sequence. In some embodiments, a Plasmodium CyRPA antigenic portion is operably linked to a heterologous signal sequence, as further described herein. In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of amino adds 30-362 of a wild-type CyRPA (SEQ ID NO: 3) or a variant thereof (e.g., a glycosylation variant). In some embedments, a Plasmodium CyRPA antigenic portion comprises or consists of a sequence according to SEQ ID NO: 133 or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of a sequence with at least 85% sequence identity to SEQ ID NO: 133 or a variant thereof (e.g., a glycosylation variant).

[0437] 30-362 portion of CyRPA (SEQ ID NO. 133)SRHVFIRTELSFIKNNVPCIRDMFFIYKRELYNICLDDLKGEEDETHIYVQKKVKDSWmLNDLFKETDLTGRPHIFAYVDVEEIIILLCE DEEFSNRKKDMTCHRFYSNDGKEYNNSEmSDYILKDKLLSSYVSLPLXIENREYFLICGVSPYKFKDDNKKDDILCMASHDKGETWGTKP / IKYDNYKLGVQYFFLRPYISKNDLSFHFYVGDNINNVKNVNFIECTHEKDLEFVCSNRDFLKDNKVLQDVSRNDEYIVSYGN DNNFAECYIFFNNENSIUKPEKYGNTTAGCYGGTFVKIDENRTLFIYSSSQGIYNIHnYYANYE

[0438] In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of amino acids 29- 362 of a wild-type CyRPA (SEQ ID NO: 3) or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of a sequence according to SEQ ID NO: 169 or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium CyRPA antigenic portion comprises orconsists of a sequence with at least 85% sequence identity to SEQ ID NO: 169 or a variant thereof (e.g., a glycosylation variant).

[0439] 29-362 portion of CyRPA (SEQ ID NO. 169)DSRHVFIRTELSFIKNNVPCIRDMFFIYKRELYNICLDDLKGEEDETHIYVQKKVKDSWrTLNDLFKETDLTGRPHIFAYVDVEEIIILLC EDEEFSNRKKDMTCHRFYSNDGKEYNNSEItISDYILKDKLLSSYVSLPLKIENREYFUCGVSPYKFKDDNKKDDILCMASHDKGETWGTKIVIKYDNYKLGVQYFFLRPYISKNDLSFHFYVGDNINNVKNVNFIECTHEKDLEFVCSNRDFLKDNKVLQDVSTLNDEYIVSYG NDNNFAECYIFFNNENSILIKPEKYGNTTAGCYGGTFVKIDENRTLFIYSSSQGIYNIHTIYYANYE

[0440] In some embodiments, one or more Plasmodium CyRPA antigenic portions comprise one or more N- llnked glycosylation sites. In some embodiments, a Plasmodium CyRPA antigenic portion comprises one, two, or three N-linked glycosylation sites. In some embodiments, a Plasmodium CyRPA antigenic portion comprises an amino acid substitution at one or more N-linked glycosylation sites, where the amino acid substitution prevents glycosylation. In some embodiments, an amino acid substitution that prevents glycosylation comprises a NX[T / S] to QX[T / S] substitution. In some embodiments, amino acid substitution prevents glycosylation comprises a NX[T / S) to NXA substitution. In some embodiments, a Plasmodium CyRPA antigenic portion comprises two amino acid substitutions at N-linked glycosylation sites that prevent glycosylation. In some embodiments, a Plasmodium CyRPA antigenic portion comprises an amino acid substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0441] In some embodiments, a Plasmodium CyRPA antigenic portion comprises an asparagine at position 145, position 322, position 338, or a combination thereof, as numbered according to SEQ ID NO: 133. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a glutamine at position 145, position 322, position338, or a combination thereof, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a glutamine at position 145, position 322, and position 338, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of an amino add sequence of SEQ ID NO: 134.

[0442] In some embodiments, a Plasmodium CyRPA antigenic portion comprises an asparagine at position 146, position 323, position 339, or a combination thereof, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a glutamine at position 146, position 323, position339, or a combination thereof, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises a glutamine at position 146, position 323, and position 339, as numbered according to SEQ ID NO: 3. In some embodiments, a Plasmodium CyRPA antigenic portion comprises or consists of an amino add sequence of SEQ ID NO: 170.

[0443] 30-362 portion of CyRPA Aolvcan (SEQ ID NO. 134)SRHVFIRTELSFIKNNVPCIRDMFFIYKRELYNICLDDLKGEEDETHIYVQKKVKDSWITLNDLFKETDLTGRPHIFAYVDVEEIIILLCE DEEFSNRKKDMTCHRFYSNDGKEYONSEITISDYILKDKLLSSYVSLPLKIENREYFLICGVSPYKFKDDNKKDDILCMASHDKGETW GTKMKYDNYKLGVQYFFLRPYISKNDLSFHFYVGDNINNVKNVNFIECTHEKDLEFVCSNRDFLKDNKVLQDVSTLNDEYIVSYGN DNNFAECYIFFNNENSILIKPEKYGOTTAGCYGGTFVKIDEORTLFIYSSSQGIYNIHTIYYANYE

[0444] 29-362 portion of CvRPA Aolvcan f SEO ID NO. 1701DSRHVFIRTELSFIKNNVPCIRDMFFIYKRELYNICLDDLKGEEDETHIYVQKKVKDSWnLNDLFKETDLTGRPHIFAYVDVEEIIILLC EDEEFSNRKKDMTCHRFYSNDGKEYONSEmSDYILKDKLLSSYVSLPLKIENREYFUCGVSPYKFKDDNKKDDILCMASHDKGETWGTKIVIKYDNYKLGVQYFFLRPYISKNDLSFHFYVGDNINNVKNVNFIECrHEKDLEFVCSNRDFLKDNKVLQDVSTLNDEYIVSYGNDNNFAECYIFFNNENSILIKPEKYGQTIAGCYGGTFVKIDEQBILFIYSSSQGIYNIHnYYANYE3. P113

[0445] In some embodiments, a Plasmodium polypeptide construct described herein Includes one or more Plasmodium Rh5 invasion complex polypeptides or portions thereof (e.g., antigenic portions thereof) that comprise one or more Plasmodium P113 polypeptides or antigenic portions thereof.

[0446] In some embodiments, a Plasmodium polypeptide construct described herein includes one or more regions or portions (e.g., antigenic portions) of a P113, e.g., Plasmodium P113, e.g., P. falciparum P113 (SEQ ID NO: 6), or a variant thereof (e.g., one or more antigenic portions of a P113, e.g., Plasmodium P113, e.g., P. falciparum P113).

[0447] In some embodiments, a Plasmodium polypeptide construct comprises one or more antigenic portion of P113. In some embodiments, a Hasmodum P113 polypeptide or antigenic portion thereof comprises 25, 30, 35, 40, or 45 contiguous amino acids of a Pl 13 polypeptide, or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium polypeptide construct comprises an antigenic portion of P113.

[0448] In some embodiments, a Plasmodium P113 antigenic portion does not comprise an endogenous signal sequence. In some embodiments, a Plasmodium P113 antigenic portion is operably linked to a heterologous signal sequence, as described further herein. In some embodiments, a Plasmodium Pl 13 antigenic portion does not comprise a GPI anchor site. In some embodiments, a Plasmodium P113 antigenic portion comprises or consists of amino acids 23-939 of a wild-type P113 (SEQ ID NO: 6) or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium P113 antigenic portion comprises or consists of a sequence according to SEQ ID NO: 135. In some embodiments, a Plasmodium P113 antigenic portion comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 135.

[0449] 23-939 portion of P113 (SEQ ID NO: 135)YVHNDVIKFGEENSLKCSQGNLYVLHCEVQCLNGNNEIIHKRCNDDIEKKCNGNNKCIYFFEYELRKKTQSFRNKNSIEISECVESEQ NEVKTSTTCLLSNSFILDEAFIQYFFFIKNKNEEPVICKDGNINIKSALLHSPFCEIKLKDISEYIRKKCDNNKECLIDPLDVQKNLLNEE DPCYINNSYVSVNWCNKEEEIGDESTDSSSMEIQDSTSNEQDENVKGMSSSQEMNSNNDENKNQDNESDDDVNNNNNNNNDD QDEQGNDGDVTSSMNKNEDNKDLEHGSSNDVNNNTDTLVNNKENKEFVLKEKSSLTSKINKELAHRTALFNKLADNISLLLNKKYD SFEIKDVLEDRYNEMKRDANPDVYYIYLMDTLDIEKIEDINLEEVKMSLLASLKETMNKIDnEKKIEEFKNKYISLYNKVKTTMPELFDLNEDLVLLYNDFPFDNGMISSDIFFKYNPSENIMDHQEMVKKGSITEDELRIVNDLEPLDNYRRRKRrTELRKILVEKLRILYLEKNNLF NTQASCIKSYCYKNPLNLKTLEVLLKKNYYRLKENKDYDWSSIIQHLDNVDANKKKKWLTHERILKKLQVLIAEGYKRINEKEKDIDR RMAVYNALYEKAQSYNLQKLFNDSNDFLKKYAIMGNSFDDGDEVFGSQSSNFNIFDSNNTDQNNEQEQPKQDDQLLNNNNDDVLS ESNNENKEKTSDDATHKETQEKSDQEPSQN1QEDNSDEKHAENEENVEQIETDSNVSEEANDENKDNMQTTTDEGTEELQQNDE DAESLTKENSKSEEQENEDSTDAEAIDKEEVETEEKGKDEQKKDEQKEQDEEEDGEKENKHKSSETTNETVTDIEENKNEVKGEEHL QGSEQSIEASESSQKDETKETEDKEEYVNANDDESSEEDTTPNE

[0450] In some embodiments, a Plasmodium P113 antigenic portion comprises one or more N-linked glycosylation sites. In some embodiments, a Plasmodium P113 antigenic portion comprises one, two, three, four, five, six, seven, or eight N-linked glycosylation sites. In some embodiments, a PlasnxxSum P113 antigenic portion comprises an amino acid substitution at one or more N-llnked glycosylation sites, where the amino add substitution prevents glycosylation. In some embodiments, an amino add substitution that prevents glycosylation comprises aNX[T / S] to QX[T / S] substitution. In some embodiments, amino add substitution prevents glycosylation comprises a NX(T / S] to NXA substitution. In some embodiments, a Plasmodium P113 antigenic portion comprises two, three, four, five, six, or seven amino acid substitutions at N-linked glycosylation sites that prevent glycosylation. In some embodiments, a Plasmodium P113 antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0451] In some embodiments, a Plasmodium P113 antigenic portion comprises an asparagine at position 207, position 268, position 317, position 360, position 661, position 697, position 779, position 876, or a combination thereof, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium P113 antigenic portion comprises a glutamine at position 207, position 268, position 317, position 360, position 661, position 697, position 779, position 876, or a combination thereof, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium P113 antigenic portion comprises a glutamine at position 207, position 268, position 317, position 360, position 661, position 697, position 779, and position 854, as numbered according to SEQ ID NO: 6. In some embodiments, a Plasmodium P113 antigenic portion comprises or consists of an amino acid sequence of SEQ ID NO: 136.

[0452] 23-939 portion of P113 Aolvcan (SEQ ID NO. 136)YVHNDVIKFGEENSLKCSQGNLYVLHCEVQCLNGNNEIIHKRCNDDIEKKCNGNNKCIYFFEYELRKKTQSFRNKNSIEISECVESEQ NEVKTSTTCLLSNSFILDEAFIQYFFFIKNKNEEPVICKDGNINIKSALLHSPFCEIKLKDISEYIRKKCDNNKECLIDPLDVQKNLLNEE DPCYIQHSYVSVNWCNKEEEIGDESTDSSSMEIQDSTSNEQDENVKGMSSSQEMNSNNDENKNQDQESDDDVNNNNNNNNDD QDEQGNDGDVTSSMNKNEDNKDLEHGSSNDVNQtnPTLVNNKENKEFVLKEKSSLTSKINKELAHRTALFNKLADQI§LLLNKKYD SFEIKDVLEDRYNEMKRDANPDVYYIYLMDRDIEKIEDINLEEVKMSLLASLKETMNKIDTIEKKIEEFKNKYISLYNKVKTTMPELFDLNEDLVLLYNDFPFDNGMISSDIFFKYNPSENIMDHQEMVKKGSnEDELRIVNDLEPLDNYRRRKRITHRKILVEKLRILYLEKNNLF NTQASCIKSYCYKNPLNLICrLEVLIKKNYYRLKENKDYDWSSIIQHLDNVDANKKKKWLTHERILKKLQVLIAEGYKRINEKEKDIDR RMAVYNALYEKAQSYNLOKLFODSNDFLKKYAIMGNSFDDGDEVFGSOSSNFNIFDSONTDONNEOEOPKODDOLLNNNNDDVL SESNNENKEKTSDDATHKETQEKSDQEPSQNIQEDNSDEKHAENEENVEQIETDSQYSEEANDENKDNMQTTTDEGTEELQQNDE DAESLTKENSKSEEQENEDSTDAEAIDKEEVETEEKGKDEQKKDEQKEQDEEEDGEKENKHKSSETTQByTDIEENKNEVKGEEHL QGSEQSIEASESSQKDETKETEDKEEYVNANDDESSEEDTTPNE 4. Ripr

[0453] In some embodiments, a Plasmodium polypeptide construct described herein includes one or more Plasmodium Rh5 invasion complex polypeptides or portions thereof (e.g., antigenic portions thereof) that comprises one or more Plasmodium Rh5-interacting Protein (Ripr) polypeptides or antigenic portions thereof.

[0454] In some embodiments, a Plasmodium polypeptide construct described herein includes one or more regions or portions (e.g., antigenic portions) of a Ripr, e.g., Plasmodium Ripr, e.g., P. falciparum Ripr (SEQ ID NO: 2), or a variant thereof (e.g., one or more antigenic portions of a Ripr, e.g., Plasmodium Ripr, e.g., P. falciparum Ripr). In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 178. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 178. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 177. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 177. In some embodiments, an antigenicportion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 176. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 176. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 175. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 175. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 174. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino acid sequence according to SEQ ID NO: 174. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 173. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 173. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 172. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 172. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 171. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 171.

[0455] 20-1086 portion of Ripr (SEQ ID NO: 171)IDUEGIFYEKNBDKLTFSLDHRVRDNlKTDLILNNNGENDYAYLNKYVYnLNRDSTEKIKTFFSHNKDMKSCDYFISKEYNSSDKTNQICYKKTECGWlPNSEBKTNKrTNDKLYCAHFNSTBlIIYYISQPLLLEPHVVYEETFFEKGKNDQINCQGMYISLRSVHVHTHNAI LQQETL1YIKNLCDGKNNCKFDFDSIKYENKSLTHYLFFINIQYQCISPLNLQENEMCDVYNDDTHKATCKYGFNKIELLKNVCEENY RCTQDICSVNQFCDGENETUTCKTSLLPSAKNNCEYNDLCTVLNCPENSTCEQIGNGKKAECKCENGKYYHNNKCYTKNDLELAIKI EPHKKEKFYKNNLYQGKALKPEYJFMQCENGFSIEVINAYVSCYRVSFNLNKLKYVTESLKKMCDGKTKCAYGNTIDPIDDLNHHNIC NNFN7IFKYDYLCVFNNQNTTSDKNSHLHSNIPSLYNSSILPDINKSKFHLISRNSRTNQYPHNNISMLBQNBSSHNSNQFSTDPHT NSNNINNMNIKKVBFRSRFSSKLQCQGGKINIDKAILKGGEGCNDLLLTNSLKSYCNDLSECDIGLIYHFDTYCINDQYLFVSYSCSN LCNKCHNNSTCYGNRFNYDCFCDNPYISKYGNKLCERPNDCESVLCSQNQVCQILPNDKLICQCEEGYKNVKGKCVPDNKCDLSCPS NKVCVIENGKQTCKCSERFVLENGVCICANDYKMEDGINCIAKNKCKRKEYENICTNPNEMCAYNEETDIVKCECKEHYYRSSRGECI LNDYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYENSCLINEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKCVLEDKC VHNKKCSENSICVNVMNKEPICVCTYNYYKKDGVCLIQNPCLXDNGGCSRNSECTFKYSKINCTCKENYKNKDDSCVPNTNEYDESF TFQYNDDASIILGACGMIEFSYTYNQIIWKINNSKESYVFYYDYPTAGNIEVQIKNEIFHTIIYLKKKIGNSVIYDDFQVDHQTCIYENV FYYSNQN

[0456] 20-1086 portion of Ripr Aolvcan (SEQ ID NO: 172)IDLIEGIFYEKNBDKLTFSLDHRVRDNLKTDLILNNNGENDYAYLNKYVYnLNRDSTEKIKTFFSHNKDMKSCDYFISKEYQSSDICr NQICYKKTFCGVVIPNSEBKrNKrTNDKLYCAHFQSTHIIIYYISQPLLLEPHVVYEETFFEKGKNDQINCQGMYISLRSVHVHTHNAI LQQETLTYIKNLCDGKNNCKFDFDSIKYEQKSLTHYLFFINIQYQCISPLNLQENEMCDVYNDDTHKATCKYGFNKIELLKNVCEENY RCTQDICSVNQFCDGEQEnnaCTSLLPSAKNNCEYNDLCTVLNCPEQSTCEQIGNGKKAECKCENGKYYHNNKCYTKNDLELAIKI EPHKKEKFYKNNLYQGKALKPEYIFMQCENGFSIEVINAYVSCYRVSFNLNKLKYVTESLKKMCDGKTKCAYGNTIDPIDDLNHHNICNNFNTIFKYDYLCVFNNQQrTSDKNSHLHSNIPSLYQSSILPDIQKSKFHLISRNSRTNQYPHNQISMLEIQNHSSHNSNQFSTDPHT NSNNINNMNIKKVBFRSRFSSKLQCQGGKINIDKAILKGGEGCNDLLLTNSLKSYCNDLSECDIGLIYHFDTYCINDQYLFVSYSCSN LCNKCHQNSTCYGNRFNYDCFCDNPYISKYGNKLCERPNDCESVLCSQNQVCQILPNDKUCQCEEGYKNVKGKCVPDNKCDLSCPS NKVCVIENGKQTCKCSERFVLENGVCICANDYKMEDGINCIAKNKCKRKEYENICTNPNEMCAYNEETDIVKCECKEHYYRSSRGECI LNDYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYENSCLINEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKCVLEDKC VHNKKCSENSICVNVMNKEPICVCTYNYYKKDGVCLIQNPCLKDNGGCSRNSECTFKYSKIQCTCKENYKNKDDSCVPNTNEYDESF TFQYNDDASIILGACGMIEFSYIYNQIIWKIQNSKESYVFYYDYPTAGNIEVQIKNEIFFrniYLKKKIGNSVIYDDFQVDHQTGIYENV FYYSNQN

[0457] 530-1086 portion of Ripr Aolvcan (SEQ ID NO: 173)LEIQNEISSHNSNQFSTDPHTNSNNINNMNIKKVEIFRSRFSSKLQCQGGKINIDKAILKGGEGCNDLLLTNSLKSYCNDLSECDIGLI YHFDTYCINDQYLFVSYSCSNLCNKCHQNSTCYGNRFNYDCFCDNPYISKYGNKLCERPNDCESVLCSQNQVCQILPNDKUCQCEE GYKNVKGKCVPDNKCDLSCPSNKVCVIENGKQTCKCSERFVLENGVCICANDYKMEDGINCIAKNKCKRKEYENICTNPNEMCAYNE ETDIVKCECKEHYYRSSRGECILNDYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYENSCUNEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKCVLEDKCVHNKKCSENSICVNVMNKEPICVCTYNYYKKDGVCLIQNPCLKDNGGCSRNSECTFKYSKIQCTC KENYKNKDDSCVPNTNEYDESFTFQYNDDASIILGACGMIEFSYIYNQIIWKIQNSKESYVFYYDYPTAGNIEVQIKNEIFHTIIYLKKK IGNSVIYDDFQVDHQTCIYENVFYYSNQN

[0458] 720-934 portion of Ripr (SEQ ID NO: 174)DLSCPSNKVCVIENGKQTCKCSERFVLENGVCICANDYKMEDGINCIAKNKCKRKEYENICTNPNEMCAYNEErDIVKCECKEHYYRS SRGECILNDYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYENSCLINEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKC VLEDKCVHNKKCSENSICVNVMNKEPICVCTYNYYKKDGVCUQ

[0459] 769-900 portion of Ripr (SEQ ID NO: 175)KNKCKRKEYENICTNPNEMCAYNEETDIVKCECKEHYYRSSRGECILNDYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECrYENSCUNEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKCVLED

[0460] 769-856 portion of Ripr (SEQ ID NO: 176)KNKCKRKEYEN1CTNPNEMCAYNEETDIVKCECKEHYYRSSRGECILNDYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYE

[0461] 817-900 portion of Ripr (SEQ ID NO: 177)DYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYENSCLINEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKCVLED

[0462] 817-856 portion of Ripr (SEQ ID NO: 178) DYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYE

[0463] In some embodiments, a Plasmodium polypeptide construct comprises one or more antigenic portions of Ripr. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises 25, 30, 35, 40, or 45 contiguous amino acids of a Ripr polypeptide, or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium polypeptide construct comprises one or more antigenic portions of Ripr.

[0464] In some embodiments, an Plasmodium Ripr antigenic portion comprises one or more N-linked glycosylation sites. In some embodiments, a Plasmodium Ripr antigenic portion comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve N-linked glycosylation sites. In some embodiments, a Plasmodium Ripr antigenic portion comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation. In some embodiments, an amino acid substitution that prevents glycosylation comprises a NX[T / S] to QX[T / S] substitution. In some embodiments, amino acid substitution prevents glycosylation comprises a NX[T / S] to NXA substitution. In some embodiments, a Plasmodium Ripr antigenic portioncomprises an amino acid substitution at all of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation.

[0465] In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises an asparagine at position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 2. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises a glutamine at position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 2. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises a glutamine at position 646, position 964, and position 1021, as numbered according to SEQ ID NO: 2. In some embodiments, the antigenic portion of a Plasmodium Ripr comprises or consists of an amino add sequence according to SEQ ID NO: 173.

[0466] 530-1086 portion of Ripr (SEQ ID NO: 190)LEIQNEISSHNSNQFSTDPHTNSNNINNMNIKKVEIFRSRFSSKLQCQGGKINIDKAILKGGEGCNDLLLTNSLKSYCNDLSECDIGLI YHFDTYCINDQYLFVSYSCSNLCNKCHNNSTCYGNRFNYDCFCDNPYISKYGNKLCERPNDCESVLCSQNQVCQILPNDKLICQCEE GYKNVKGKCVPDNKCDLSCPSNKVCVIENGKQTCKCSERFVLENGVCICANDYKMEDGINCIAKNKCKRKEYENICTNPNEMCAYNE ETDIVKCECKEHYYRSSRGECILNDYCKDINCKENEECSIVNFKPECVCKENLKKNNKGECIYENSCLINEGNCPKDSKCIYREYKPHECVCNKQGHVAVNGKCVLEDKCVHNKKCSENSICVNVMNKEPICVCnrNYYKKDGVCLIQNPCLKDNGGCSRNSECTFKYSKINCTCK ENYKNKDDSCVPNTNEYDESFTFQYNDDASIILGACGMIEFSYIYNQIIWKINNSKESYVFYYDYPTAGNIEVQIKNEIFHTIIYLKKKI GNSVIYDDFQVDHQTCIYENVFYYSNQN

[0467] In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises an asparagine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, position 1021, or a combination thereof, as numbered accordng to SEQ ID NO: 2. In some embodiments, an antigenic portion of a Pfasmodium Ripr polypeptide comprises a ^utamine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, position 1021, or a combination thereof, as numbered according to SEQ ID NO: 2. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises a glutamine at position 103, position 144, position 228, position 303, position 334, position 480, position 498, position 506, position 526, position 646, position 964, and position 1021, as numbered according to SEQ ID NO: 2. In some embodiments, an antigenic portion of a Plasmodium Ripr polypeptide comprises or consists of SEQ ID NO: 172.

[0468] In some embodiments, a Plasmodium Ripr antigenic portion comprises a PMX cleavage site. In some embodiments, a PMX cleavage site of a Ripr antigenic portion comprises a sequence of GNISMLEIQNEE (SEQ ID NO: 37). In some embodiments, a Plasmodium Ripr antigenic portion does not comprise a PMX cleavage site. In some embodiments, a PMX cleavage site of a Ripr antigenic portion comprises or consists of a sequence of SMLE (SEQ ID NO: 191).5. TRAMPsome embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 179. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 179.

[0471] 42-352 portion of TRAMP (SEQ ID NO: 179)LQVYQNNGNFKMEILEPECT1QKNLPSEEEKEEFIDFDRKELLLHDFWIKNSQFTDEKTLELYLSKEENNKSYLMLTFYLGDLKLMIG HNSPYEISLILNVATVNKNMSNCKNNSYNIVLLIGTDVFNTSDLEILEGPIQFSLGKSSGAFRINVTNFFLNNTWKAFTKDKISFLIKPE ENCYTILENKINKPQLLIEKICrTFYSEWGEWSNCSMDCDHPDNVQIRERECIHPSGDCFKGDLKESRPCIPLPPCNELFSHKDNSTF KILMIILPIVLVISimLYHIFYKRKGAEKELYENVAGRYMYD

[0472] In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises 25, 30, 35, 40, or 45 contiguous amino acids of a TRAMP polypeptide, or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium polypeptide construct comprises an antigenic portion of TRAMP.

[0473] In some embodiments, a Plasmodium TRAMP antigenic portion comprises one or more N-linked glycosylation sites. In some embodiments, a Plasmodium TRAMP antigenic portion comprises one, two, three, four, five, six, seven, or eight N-linked glycosylation sites. In some embodiments, a PlasmodiumTRMAP antigenic portion comprises an amino acid substitution at one or more N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation. In some embodiments, an amino add substitution that prevents glycosylation comprises a NX[T / S] to QX[T / S] substitutlon. In some embodiments, amino add substitution prevents glycosylation comprises a NX[T / S] to NXA substitution. In some embodiments, a Plasmodium TRAMP antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino acid substitution prevents glycosylation.

[0474] In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptidecomprises an asparagine at position 149, position 195, position 202, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a glutamine at position 149, position 195, position 202, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a glutamine at position 149, position 195, and position 202, as numbered according to SEQ ID NO: 4. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 181.

[0475] 42-352 portion of TRAMP Aolvcan (SEQ ID NO: 181)LQVYQNNGNFKMEILEPECnQKNLPSEEEKEEnDFDRKELLLHDFWIKNSQFTDEKTLELYLSKEENNKSYLMLTFYLGDLKLMIG HNSPYEISLILNVATVNKQMSNCKNNSYNIVLLIGTDVFNTSDLEILEGPIQFSLGKSSGAFRIQVTNFFLQNTWKAFTKDKISFLIKPE ENCYnLENKINKPQLUEKKTTFYSEWGEWSNCSMDCDHPDNVQIRERECIHPSGDCFKGDLKESRPCIIPLPPCNELFSHKDNSTF KILMIILPIVLVISimLYHIFYKRKGAEKELYENVAGRYMYD

[0476] In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises an asparagine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, position 305, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a glutamine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, position 305, or a combination thereof, as numbered according to SEQ ID NO: 4. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a glutamine at position 112, position 149, position 155, position 170, position 195, position 202, position 253, and position 305, asnumbered according to SEQ ID NO: 4. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 180.

[0477] 42-352 portion of TRAMP Aolvcen (SEQ ID NO: 180)LQVYQNNGNFKMEILEPECnQKNLPSEEEKEEFIDFDRKELLLHDFVVIKNSQFTDEKTLELYLSKEENQKSYLMLTFYLGDLKLMIG HNSPYEISLILNVATVNKQMSNCKQNSYNIVLLJGTDVFQTSDLEILEGPIQFSLGKSSGAFRIQVrNFFLQNTWKAFTKDKISFLIKPE ENCYTILENKINKPQLLIEKICTTFYSEWGEWSQCSMDCDHPDNVQIRERECIHPSGDCFKGDLKESRPCIIPLPPCNELFSHKDQSTF KUMHLPIVLVISimLYHIFYKRKGAEKELYENVAGRYMYD

[0478] In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a PMX cleavage site. In some embodiments, a PMX cleavage site of TRAMP antigenic portion comprises or consists of a sequence of HFLQ (SEQ ID NO: 192). In some embodiments, an antigenic portion of a PlasmodkimlRMAP polypeptide comprises a SUB2 cleavage site. In some embodiments, a SUB2 cleavage site of TRAMP antigenic portion comprises or consists of ILMIILPIVLVISimLYHIFY (SEQ ID NO: 193).

[0479] In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a transmembrane region (also referred to as a "transmembrane domain”). In some embodiments, an antigenic portion of a PiasmodiumTWM? polypeptide comprises a transmembrane region at the C-terminus. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a HSV transmembrane region, e.g., an HSV-1 or HSV-2 transmembrane region. In some embodiments, an antigenic portion of a Plasmodium TRAMP polypeptide comprises a transmembrane region that comprises or consists of an HSV gD transmembrane region, e.g., comprising or consisting of an amino add sequence of SEQ ID NO:75. In some embodiments, a Plasmodium TRAMP polypeptide does not comprise a transmembrane region.6. CSS

[0480] In some embodiments, a Plasmodium polypeptide construct described herein Includes one or more Plasmodium Rh5 Invasion complex polypeptides or portions thereof (e.g., antigenic portions thereof) that comprises one or more Plasmodium cysteine-rich small secreted protein (CSS) polypeptides or antigenic portions thereof.

[0481] In some embodiments, a Plasmodium polypeptide construct described herein includes one or more regions or portions of a CSS, e.g., Plasmodium CSS, e.g., P. falciparum CSS (SEQ ID NO: 5 or 214), or a variant thereof (e.g., one or more antigenic portions of a CSS, e.g., Plasmodium CSS, e.g., P. falciparum CSS").

[0482] In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises a C30S mutation, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises a serine at position 30, as numbered according to SEQ ID NO: 5 or 214.

[0483] In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises or consists of an amino acid sequence with at least 85% sequence Identity to an amino acid sequence according to SEQ ID NO: 194. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 194. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 195. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 195. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 182. In some embodiments, an antigenicportion of a Plasmodium CSS polypeptide comprises or consists of an amino add sequence according to SEQ ID NO: 182.

[0484] 21-152 portion of CSS (SEQ ID NO: 194)QDEKSVKNISVCDfTDKLNFLPLEKTKILCELKPQYGEDIKIIANKEYEINCMNNSKVFSPLKDTFINMTNIKLYSPKLHFEIKDITHKGK NAALYYLKIDEEASDIFFSCSIKPKQVSGLLEGEVRVNLKK

[0485] 153-290 portion of CSS (SEQ ID NO: 195)HINEEYSIFNEEEDVHVCDFSKGNLDUPSAGFYLKNSRNVSCIYRVIPNKLFUKLPKLDIVTEKLLPSIVNCLSEFSHNFTLKHVQEG DNYISFNVIFGEFKKHFNLTCSLDLSDFQQEPSNLGKTANITFIFSK

[0486] 21-290 portion of CSS (SEQ ID NO: 182)QDEKSVKNISVCDFTDKLNFLPLEKTKILCELKPQYGEDIKIIANKEYEINCMNNSKVFCPLKDTFINNTNIKLYSPKLHFEIKDITHKGK NAALYYLKIDEEASDIFFSCSIKPKQVSGLLEGEVRVNLKKHINEEYSIFNEEEDVHVCDFSKGNLDITPSAGFYLKNSRNVSCIYRVIP NKLFLIKLPKLDIVTEKLLPSIVNCLSEFSnNFTLKHVQEGDNYISFNVIFGEFKKHFNLTCSLDLSDFQQEPCNLGKTANnrHFSK

[0487] In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises 25, 30, 35, 40, or 45 contiguous amino acids of a CSS polypeptide, or a variant thereof (e.g., a glycosylation variant). In some embodiments, a Plasmodium polypeptide construct comprises one or more antigenic portions of CSS.

[0488] In some embodiments, a Plasmodium CSS antigenic portion comprises one or more N-linked glycosylation sites. In some embodiments, a Plasmodium CSS antigenic portion comprises one, two, three, four, five, or six N-linked glycosylation sites. In some embodiments, a Plasmodium CSS antigenic portion comprises an amino add substitution at one or more N-llnked glycosylation sites, where the amino add substitution prevents glycosylation. In some embodiments, an amino acid substitution that prevents glycosylation comprises a NX[T / S] to QX[T / S] substitution. In some embodiments, amino acid substitution prevents glycosylation comprises a NX[T / S] to NXA substitution. In some embodiments, a Plasmodium CSS antigenic portion comprises an amino add substitution at all of the N-linked glycosylation sites, wherein the amino add substitution prevents glycosylation.

[0489] In some embodiments, an antigenic portion of Plasmodium CSS polypeptide comprises a serine at position 80, as numbered according to SEQ ID NO: 5 or 214.

[0490] In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises an asparagine at position 74, position 88, or a combination thereof, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises a glutamine at position 74, position 88, or a combination thereof, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises a glutamine at position 74, and position 88, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises or consists of an amino acid sequence according to SEQ ID NO: 184.

[0491] 21-152 portion of CSS Advcan (SEQ ID NO: 184)QDEKSVKNISVCDFTDKLNFLPLEKTKILCELKPQYGEDIKIIANKEYBNCMQNSKVFSPLKDTFIQNTNIKLYSPKI-HFEIKDITHKGK NAALYYLKIDEEASDIFFSCSIKPKQVSGLLEGEVRVNLKK

[0492] In some embodiments, an antigenic portion of Plasmodium CSS polypeptide comprises a serine at position 276, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises an asparagine at position 192, position 234, position 261, position 283, or a combination thereof, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises a glutamine at position 192, position 234, position 261, position 283, or acombination thereof, as numbered according to SEQ ID NO: 5 or 214. In some embodiments, an antigenic portion of a Plasmodium CSS polypeptide comprises a glutamine at position 192, position 234, position 261, and position 283, as numbered acco...

Claims

CLAIMS1. A polyribonudeotide encoding a polypeptide, wherein the polypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof.

2. The polyribonudeotide of daim 1, wherein the one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof comprise:(i) one or more Plasmodium reticulocyte-binding protein homolog 5 (Rh5) polypeptides or antigenic portions thereof;(ii) one or more / Vasma / Ajm Cysteine-Rich Protective Antigen (CyRPA) polypeptides or antigenic portions thereof;(iii) one or more Plasmodium Rh5-interacting Protein (Ripr) polypeptides or antigenic portions thereof;(iv) one or more Plasmodium P113 polypeptides or antigenic portions thereof;(v) one or more Plasmodium thrombospondin-related apical merozoite protein (TRAMP) polypeptides or antigenic portions thereof; or(vi) one or more Plasmodium cysteine-rich small secreted protein (CSS) polypeptides or antigenic portions thereof.

3. The polyribonudeotide of daim 2, wherein the one or more Plasmodium Rh5 antigenic portions comprise:(i) an amino add sequence according to SEQ ID NO: 118, 119, 124, or 126,(II) an amino add sequence according to SEQ ID NO: 120 or 128, or(III) a combination thereof.

4. The polyribonudeotide of daim 2, wherein the one or more Plasmodium Rh5 antigenic portions comprise:(I) an amino add sequence according to SEQ ID NO: 121, 122, 125, or 127, (ii) an amino acid sequence according to SEQ ID NO: 123 or 129, or (Hi) a combination thereof.

5. The polyribonudeotide of any one of claims 1-2, wherein the one or more Plasmodium Rh5 antigenic portions comprise:(i) an amino add sequence according to SEQ ID NO: 124, 125, 126, or 127,(ii) an amino acid sequence according to SEQ ID NO: 128 or 129, or(III) a combination thereof.

6. The polyribonudeotide of daim 2, wherein the one or more Plasmodium Rh5 antigenic portions comprise:(i) an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 130,(ii) an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 118, 119, 121, 122, 124, 125, 126, or 127,(iii) an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 131,(iv) an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 120, 123, 128, or 129, or(v) a combination thereof.

7. The polyribonucleotide of any one of claims 1-2, wherein the polypeptide comprises an amino add sequence with at least 85% sequence identity to an amino add sequence of positions 26-363 of SEQ ID NO: 94, 95 or 99.

8. The polyribonudeotide of any one of claims 1-2, wherein the polypeptide comprises an amino add sequence with at least 85% sequence identity to an amino add sequence of positions 26-526 of SEQ ID NO: 89.

9. The polyribonudeotide of claim 1 or 2, wherein the one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof comprise a Plasmodium CyRPA polypeptide or antigenic portion thereof.

10. The polyribonudeotide of dalm 1 or 2, wherein the one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof comprise a Plasmodium P113 polypeptide or antigenic portions thereof.

11. The polyribonudeotide of dalm 1 or 2, wherein the one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof comprise a Plasmodium Ripr polypeptide or antigenic portion thereof.

12. The polyribonudeotide of dalm 1 or 2, wherein the one or more Plasmodium Rh5 Invasion complex polypeptides or antigenic portions thereof comprise a Plasmodium TRAMP polypeptide or antigenic portion thereof.

13. The polyribonudeotide of dalm 1 or 2, wherein the one or more Plasmodium Rh5 Invasion complex polypeptides or antigenic portions thereof comprise a Plasmodium CSS polypeptide or antigenic portion thereof.

14. The polyribonudeotide of dalm 1 or 2, wherein the polypeptide comprises(I) a secretory signal, and(II) two Piasmodum Rh5 ordered domains.

15. The polyribonudeotide of dalm 1 or 2, wherein the polypeptide comprises(I) a secretory signal,(II) two Plasmodium Rh5 ordered domains,(iii) a linker, and(iv) a multimerization domain.

16. The polyribonudeotide of dalm 1 or 2, wherein the polypeptide comprises(I) a secretory signal,(II) two Piasmodum Rh5 ordered domains,(iii) a linker, and(Iv) a transmembrane region.

17. The pdyribonudeotide of daim 1 or 2, wherein the polypeptide comprises(i) a secretory signal,(ii) two Plasmodium Rh5 ordered domains,(iii) a linker, and(iv) a self-assembling nanopartide domain.

18. The pdyribonudeotide of any one of daims 14-17, wherein the polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 94.

19. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 90.

20. The pdyribonudeotide of any one of daims 14-17, wherein the polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 92.

21. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 96.

22. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 99.

23. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino acid sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 98.

24. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 101.

25. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 100.

26. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino add sequence with at least 85% sequence Identity to an amino add sequence according to SEQ ID NO: 95.

27. The pdyribonudeotide of any one of daims 14-17, wherein the pdypeptide comprises or consists of an amino add sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 91.

28. The pdyribonudeotide of any one of claims 14-17, wherein the pdypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 93.

29. The polyribonucleotide of any one of claims 14-17, wherein the polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino acid sequence according to SEQ ID NO: 97.

30. The polyribonucleotide of claim 1 or 2, wherein the polypeptide comprises(i) a secretory signal,(ii) a Plasmodium Rh5 N-terminal disordered domain,(iii) a Plasmodium Rh5 ordered domain,(iv) a Plasmodium Rh5 linking disordered domain, and(v) a Plasmodium Rh5 C-terminal ordered domain.

31. The polyribonucleotide of claim 30, wherein the polypeptide comprises or consists of an amino acid sequence with at least 85% sequence identity to an amino add sequence according to SEQ ID NO: 89.

32. An RNA construct comprising in 5* to 3' order:(0 a 5' UTR;(ii) a polyribonucleotide of any one of claims 1-532;(Hi) a 3' UTR; and(iv) a polyA tail sequence.

33. A composition comprising one or more polyribonucleotides of any one of claims 1-31.

34. A composition comprising one or more RNA constructs of claim 32.

35. The composition of claim 33 or 34, wherein the composition further comprises lipid nanopartides, polyplexes (PLX), lipidated polyplexes (LPLX), or liposomes, wherein the one or more polyribonucleotides are fully or partially encapsulated within the lipid nanoparticles, polyplexes (PLX), lipidated polyplexes (LPLX), or liposomes.

36. A pharmaceutical composition comprising the composition of claim 35 and at least one pharmaceutically acceptable excipient.

37. A combination comprising:(I) a first pharmaceutical composition comprising a first pdyribonudeotide, wherein the first polyribonucleotide encodes a first polypeptide, and the first polypeptide comprises one or more Plasmodium Rh5 polypeptides or antigenic portions thereof; and(ii) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide encodes a second polypeptide, the second polypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides selected from: one or more CyRPA polypeptides or antigenic portions thereof, one or more Ripr polypeptides or antigenic portions thereof,one or more Pl 13 polypeptides or antigenic portions thereof, one or more TRAMP polypeptides or antigenic portions thereof, one or more CSS polypeptides or antigenic portions thereof, or a combination thereof.

38. A combination comprising:(i) a first pharmaceutical composition comprising a first polyribonucleotide polyribonucleotide of any one of claims 1-31, wherein the first polyribonucleotide encodes a first polypeptide, and the first polypeptide comprises one or more Piasmtxfium Rh5 invasion complex polypeptides or antigenic portions thereof; and(II) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide encodes a second polypeptide, the second polypeptide comprises one or more PlasmodiumT cell antigens.

39. A combination comprising:(i) a first pharmaceutical composition comprising a first polyribonucleotide of any one of claims 1-31, wherein the first polyribonucleotide encodes a first polypeptide, and the first polypeptide comprises one or more Plasmodium Rh5 invasion complex polypeptides or antigenic portions thereof; and(il) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide encodes a second polypeptide, the second polypeptide comprises one or more Plasmodium C.SP polypeptides or antigenic portions thereof.

40. A method comprising administering a polyribonucleotide according to any one of claims 1-31 to a subject41. A method comprising administering an RNA construct according to claim 32 to a subject.

42. A method comprising administering a composition according to any one of claims 33-35 to a subject.

43. A method comprising administering one or more doses of the pharmaceutical composition of claim 36 to a subject44. The pharmaceutical composition of claim 36 for use in the treatment of a malaria infection comprising administering one or more doses of the pharmaceutical composition to a subject45. The pharmaceutical composition of claim 36 for use in the prevention of a malaria infection comprising administering one or more doses of the pharmaceutical composition to a subject46. A method comprising administering a combination of any one of claims 37-39 to a subject.

47. Use of the pharmaceutical composition of claim 36 in the treatment of a malaria infection.

48. Use of the pharmaceutical composition of claim 36 in the prevention of a malaria infection.

49. Use of the pharmaceutical composition of claim 36 in inducing an anti-malaria immune response in a subject50. A polypeptide encoded by a polyribonucleotide of any one of claims 1-31.

51. A polypeptide encoded by an RNA construct of claim 32.

52. A host cell comprising a polyribonucleotide of any one of claims 1-31.

53. A host cell comprising an RNA construct of claim 32.

54. A host cell comprising a polypeptide of claim 50 or 51.

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